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Aim: To explore how introduction of the lower WHO gestational diabetes (GDM) glucose criteria in Sweden affected prediabetes/type-2-diabetes (T2D) incidence two years postpartum., Methods: Women included in the PREvention of PostPartum (PREPP) diabetes study were diagnosed with GDM according to EASD 1991 criteria (GDM OLD ; n = 93) or only WHO 2013 criteria (GDM WHO ; n = 174). Both groups were further stratified by BMI, and BMI-matched normoglycemic pregnancy controls were included (n = 88). Postpartum assessments included oral glucose tolerance tests (OGTT) and anthropometric measurements., Results: There was a higher postpartum incidence of T2D in GDM OLD versus GDM WHO (P < 0.001). Despite similar BMI, GDM OLD exhibited higher fasting and OGTT glucose levels, lower fat-free-mass, and hip circumference compared to GDM WHO . In normal-weight women, both GDM groups displayed higher HOMA-IR and lower fat-free-mass compared to controls, with GDM OLD additionally showing lower HOMA-β, slower insulin release during OGTT, and worse glucose tolerance than GDM WHO . Among obese women, the main differences were lower fat-free-mass and hip circumference in GDM OLD ., Conclusion: The lower glucose cut-offs during pregnancy resulted in lower postpartum incidence of T2D, irrespective of BMI. Fat-free-mass emerged as a key determinant in glucose levels across BMI categories, while lower beta-cell function played a significant role in normal-weight women., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ulrika Andersson-Hall reports financial support was provided by Emil and Wera Cornell Foundation. Agneta Holmang reports financial support was provided by The Swedish state under the ALF agreement between the Swedish government and the county councils. Verena Sengpiel reports financial support was provided by The Swedish state under the ALF agreement between the Swedish government and the county councils. Ulrika Andersson-Hall reports financial support was provided by Tore Nilson Foundation for Medical Research. Ulrika Andersson-Hall reports financial support was provided by Erik & Lily Philipsons foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: The objective of this study was to evaluate retinal sensitivity in subfields and its association with the novel quantitative contrast sensitivity function (qCSF) in patients with early age-related macular degeneration (eAMD), in patients with intermediate AMD (iAMD), and in healthy controls., Methods: In this prospective longitudinal study, retinal sensitivity of a customized 24-point grid was assessed by microperimetry Macular Integrity Assessment (MAIA, CenterVue, Padova, Italy) and divided into different subfields. The Multiple Contrast Vision Meter (Adaptive Sensory Technology, San Diego, CA, USA) was used for qCSF testing. Linear models were used to test the association of functional metrics with variables of interest., Results: 92 study eyes from 92 participants were analyzed (13 eAMD, 31 iAMD, and 48 controls). Microperimetry subfield comparison showed significant differences (p &lt; 0.0001) in the control group between superior and inferior hemifield as well as between central and peripheral subfields. For eAMD, significant differences were found between central and peripheral subfields (p &lt; 0.001) and specific subfields (p &lt; 0.05) and finally for iAMD between specific quadrants (p &lt; 0.05) and specific squares (p &lt; 0.05). Significant associations of retinal sensitivity with qCSF metrics were found for the area underneath the logarithmic contrast sensitivity function, contrast acuity and for the contrast sensitivity at specific spatial frequencies., Conclusions: This study showed significant differences in the evaluated retinal sensitivity subfields, providing localized natural history data for retinal sensitivity in healthy controls and patients with eAMD and iAMD., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Purpose: The purpose of this study was to describe, validate, and compare the contrast sensitivity functions (CSFs) acquired with the novel quick CSF (qCSF) method from patients with early and intermediate age-related macular degeneration (eAMD and iAMD) and healthy controls., Methods: This is a cross-sectional analysis of contrast sensitivity (CS) and visual acuity (VA) baseline data from the prospective Multimodal Functional and Structural Visual System Characterization (MUMOVI) study. The qCSF testing was conducted with the manifold contrast vision meter (Adaptive Sensory Technology, San Diego, CA, USA). CS levels at spatial frequencies from 1 cycle per degree (CPD) to 18 CPD, the area underneath the logarithmic contrast sensitivity function (AULCSF), and contrast acuity (CA) were analyzed. The association of functional metrics with variables of interest was tested with linear models., Results: Ninety-four study eyes from 94 study patients were included in the analysis (13 patients with eAMD, 33 patients with iAMD, and 48 healthy controls). Significant differences between the eAMD and the iAMD model estimates were only found for CS at 1 CPD (t value = -2.9, P value = 0.006) and CS at 1.5 CPD (-2.7, 0.01). A specific association between smoking years and CS at 1 CPD (P = 0.02) and CS at 1.5 CPD (P = 0.03) could be described in patients with AMD., Conclusions: The qCSF testing allows the fast measurement of the whole CSF, enabling the integration into clinical routine. We showed that novel qCSF-derived metrics detect slight functional differences between AMD stages, which testing by Pelli-Robson charts or VA testing would miss. This study, therefore, yields novel qCSF-derived candidate metrics for therapeutic trials in AMD.

A gestational diabetes mellitus (GDM) diagnosis during pregnancy means an increased risk of developing type 2 diabetes later in life. By following up with women after GDM we aimed to examine the relationship between iron parameters, individual fatty acids (FAs) and desaturases in the development of impaired glucose metabolism (IGM). Based on an oral glucose tolerance test (OGTT), six years after GDM, 157 women were grouped as having normal glucose tolerance (NGT) or IGM. Fasting serum FAs, activity of desaturases and iron parameters (ferritin, transferrin, iron, soluble transferrin receptor, total iron binding capacity, hepcidin) were measured, and clinical and anthropometric measurements taken. Soluble transferrin receptor was higher in the IGM group compared to the NGT group (3.87 vs. 3.29 mg/L, p -value = 0.023) and associated positively with saturated FAs and negatively with monounsaturated FAs in the IGM group (adjusted for BMI, age and high sensitivity C-reactive protein; p -value < 0.05). Iron, as well as transferrin saturation, showed a positive association with MUFAs and desaturase activity. These associations were not seen in the NGT group. These results suggest that iron homeostasis and FA metabolism interact in the development of glucose intolerance in women with previous GDM.

Background: Commercial activity trackers are increasingly used in research and compared with research-based accelerometers are often less intrusive, cheaper, with improved storage and battery capacity, although typically less validated. The present study aimed to determine the validity of Oura Ring step-count and energy expenditure (EE) in both laboratory and free-living., Methods: Oura Ring EE was compared against indirect calorimetry in the laboratory, followed by a 14-day free-living study with 32 participants wearing an Oura Ring and reference monitors (three accelerometers positioned at hip, thigh, and wrist, and pedometer) to evaluate Oura EE variables and step count., Results: Strong correlations were shown for Oura versus indirect calorimetry in the laboratory (r = 0.93), and versus reference monitors for all variables in free-living (r ≥ 0.76). Significant (p < 0.05) mean differences for Oura versus reference methods were found for laboratory measured sitting (- 0.12 ± 0.28 MET), standing (- 0.27 ± 0.33 MET), fast walk (- 0.82 ± 1.92 MET) and very fast run (- 3.49 ± 3.94 MET), and for free-living step-count (2124 ± 4256 steps) and EE variables (MET: - 0.34-0.26; TEE: 362-494 kcal; AEE: - 487-259 kcal). In the laboratory, Oura tended to underestimate EE with increasing discrepancy as intensity increased. The combined activities and slow running in the laboratory, and all MET placements, TEE hip and wrist, and step count in free-living had acceptable measurement errors (< 10% MAPE), whereas the remaining free-living variables showed close to (≤13.2%) acceptable limits., Conclusion: This is the first study investigating the validity of Oura Ring EE against gold standard methods. Oura successfully identified major changes between activities and/or intensities but was less responsive to detailed deviations within activities. In free-living, Oura step-count and EE variables tightly correlated with reference monitors, though with systemic over- or underestimations indicating somewhat low intra-individual validity of the ring versus the reference monitors. However, the correlations between the devices were high, suggesting that the Oura can detect differences at group-level for active and total energy expenditure, as well as step count., (© 2023. The Author(s).)

Aims: We sought to identify self-reported exercise and objectively measured fitness variables associated with glucose tolerance and metabolic health 6-10 years after gestational diabetes (GDM) METHODS: Women (n = 84) underwent oral glucose tolerance testing (OGTT), body composition measurements, and lifestyle questionnaires 6 and 10 years after GDM. In a subset (n = 45), peak oxygen uptake (VO 2peak ), peak fat oxidation, and maximal isometric strength of five muscle groups were tested., Results: At 10 years, 41 women (49%) had impaired glucose metabolism or type 2 diabetes (T2D). VO 2peak and muscle strength were lowest in the T2D group. In a regression analysis, VO 2peak and all strength measurements were associated negatively with HbA1c and waist-hip ratio and positively with high-density lipoprotein cholesterol. However, only muscle strength was associated with fasting and area-under-the-curve glucose. For changes between the 6- and 10-year follow-ups, only muscle strength was associated with HbA1c change, whereas both VO 2peak and strength were associated with high-density lipoprotein level and changes in waist-hip ratio. Peak fat oxidation and self-reported physical activity showed no or weak relationships with glycemic variables., Conclusion: Objectively measured fitness variables, particularly muscle strength, were strongly associated with glycemic and other metabolic outcomes in a high-risk group after GDM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Scientists who work on bioinspired systems may see the potential for products resulting from their research, but are often unaware of the various steps or issues related to commercialization or product development. Commercialization topics lie outside the usual training of a basic biologist, and therefore much of their exposure to these topics is adventitious, such as from casual conversations at meetings. Thus, the information gleaned may be somewhat piecemeal. In this paper, I briefly summarize some of what I have learned over the last ten years about commercialization from a variety of different sources, related to a bioinspired project in which I am involved. My collaborators and I have invented and patented a technology to entrap insect pests by a purely physical mechanism (a "physical insecticide" that does not involve a chemical insecticide). This bioinspired technology is based on a historical control method, in which leaves from bean plants were used to capture bed bugs for hundreds of years in parts of Eastern Europe. Sharp recurved microstructures (nonglandular trichomes) on the leaf surfaces irreversibly impale the tarsi (feet) of the bed bugs as they walk over the surfaces, trapping them in place. Pest professionals have identified bed bugs as the most difficult pest to control; there is a clear need for new methods of control for this pest. There are societal benefits and consumer demand for products that are sustainable, without regulatory constraints, and that minimize insecticide exposure for humans. But how would these products be developed from this starting point of a bioinspired invention? I will briefly share some of our experiences in the early and ongoing product development of entrapping surfaces, with the hope that this might interest or aid others who are considering entrepreneurial activities. Unfamiliar topics such as intellectual property, customer segmentation, value propositions, business models, conflict of interest, and conflict of commitment may require some attention from prospective entrepreneurs. This brief and introductory overview is intended for those academic scientists with little to no experience or knowledge in the area of commercialization., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.)

Objective/aim: Growth-differentiation-factor 15 (GDF15) has been suggested to improve or protect beta cell function. During pregnancy, beta cell numbers and function increase to overcome the natural rise in insulin resistance during gestation. In this study, we longitudinally measured serum GDF15 levels during and after pregnancy in women of normal weight (NW) and in women with obesity (OB) and explored associations between GDF15 and changes in beta cell function by homeostatic model assessment (HOMA)., Methods: The cohort participants were 38 NW (BMI 22.3 ± 1.7) and 35 OB (BMI 35.8 ± 4.2). Blood was sampled and body composition measured at each trimester (T1, T2, and T3) and at 6, 12 and 18 months postpartum. Fasting glucose, insulin and GDF15 were measured, and HOMA for insulin resistance (HOMA-IR) and beta cell function (HOMA-B) determined., Results: GDF15 levels increased significantly each trimester and were ~200-fold higher at T3 than in the nonpregnant postpartum state. GDF15 was higher in NW than OB during pregnancy, but was reversed after pregnancy with a significant interaction effect. GDF15 correlated inversely with BMI and fat-free mass at T3. Low GDF15 was associated with lower incidence of nausea and with carrying a male foetus. The pregnancy induced increase in GDF15 associated with increased HOMA-B in OB and with reduced fasting glucose in all women., Conclusion: Large gestational upregulation of GDF15 levels may help increase insulin secretory function to overcome pregnancy-induced insulin resistance., (© 2021 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

Adipose tissue and adipokine concentrations change markedly during pregnancy, but the effects of physical activity on these changes are rarely studied. We aimed to assess physical activity levels in pregnant women of normal-weight (NW) or with obesity (OB), and to determine the relation with changes in fat mass and adipokines. In each trimester, pregnant women (136 NW, 51 OB) were interviewed about their physical activity and had their body composition, leptin, soluble leptin receptor (sOB-R) and adiponectin determined. NW reported higher activity and more aerobic exercise than OB during early pregnancy. Both groups maintained training frequency but reduced overall activity as pregnancy progressed. NW women reporting aerobic and/or resistance exercise and OB women reporting aerobic exercise had greater sOB-R increases (independent of BMI or gestational weight gain). In NW, exercise also associated with lower fat mass and leptin increases. Higher activity levels associated with lower gestational weight gain in both groups. The relationship between physical activity and adiponectin differed between NW and OB. Maternal exercise may partly mediate its beneficial effects through regulation of leptin bioavailability, by enhancing pregnancy-induced increases in sOB-R. This could be of particular importance in OB with pre-gestational hyperleptinemia and leptin resistance.

Aim: Growth differentiation factor 15 (GDF15) increases in serum during pregnancy to levels not seen in any other physiological state and is suggested to be involved in pregnancy-induced nausea, weight regulation and glucose metabolism. The main action of GDF15 is regulated through a receptor of the brainstem, i.e., through exposure of GDF15 in both blood and cerebrospinal fluid (CSF). The aim of the current study was to measure GDF15 in both CSF and serum during pregnancy, and to compare it longitudinally to non-pregnant levels., Methods: Women were sampled at elective caesarean section (n = 45, BMI = 28.1±5.0) and were followed up 5 years after pregnancy (n = 25). GDF15, insulin and leptin were measured in CSF and serum. Additional measurements included plasma glucose, and serum adiponectin and Hs-CRP., Results: GDF15 levels were higher during pregnancy compared with follow-up in both CSF (385±128 vs. 115±32 ng/l, P<0.001) and serum (73789±29198 vs. 404±102 ng/l, P<0.001). CSF levels correlated with serum levels during pregnancy (P<0.001), but not in the non-pregnant state (P = 0.98). Both CSF and serum GDF15 were highest in women carrying a female fetus (P<0.001). Serum GDF15 correlated with the homeostatic model assessment for beta-cell function and placental weight, and CSF GDF15 correlated inversely with CSF insulin levels., Conclusion: This, the first study to measure CSF GDF15 during pregnancy, demonstrated increased GDF15 levels in both serum and CSF during pregnancy. The results suggest that effects of GDF15 during pregnancy can be mediated by increases in both CSF and serum levels., Competing Interests: We have read the journal’s policy and the authors of this manuscript have the following competing interests: KB has served as a consultant, at advisory boards, or at data monitoring committees for Abcam, Axon, Biogen, JOMDD/Shimadzu. Julius Clinical, Lilly, MagQu, Novartis, Roche Diagnostics, and Siemens Healthineers, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program. HZ has served at scientific advisory boards for Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics and CogRx, has given lectures in symposia sponsored by Fujirebio, Alzecure and Biogen, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). The other authors declare no conflict of interest. These potential conflicts do not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Protein availability around aerobic exercise might benefit aerobic capacity and body composition in normal weight adults. However, it is unknown if individuals with overweight/obesity elicit similar adaptations or improve other cardiometabolic/health-related markers in response to different types of protein. Thus, our aim was to study the effect of supplementation of two different protein drinks in conjunction with exercise on aerobic capacity, body composition and blood health markers in untrained subjects with overweight or obesity. Methods: The present study measured training adaptation and health parameters over a 6 week period in untrained men with overweight/obesity ( n = 28; BMI 30.4 ± 2.2 kg/m 2 ) ingesting either plant- (Oat/Potato; n = 8) or animal-based (Milk; n = 10) protein-carbohydrate drinks (10 g of protein/serving), or a control carbohydrate drink ( n = 10) acutely before and after each training session (average three sessions/week @ 70% HR max ). Pre-post intervention V ˙ O 2 peak , muscle biopsies and blood samples were collected, body composition measured (DXA) and two different exercise tests performed. Body weight was controlled with participants remaining weight stable throughout the intervention. Results: For the groups combined, the training intervention significantly increased V ˙ O 2 peak (8%; P < 0.001), performance in a time-to-exhaustion trial (~ 100%; P < 0.001), mitochondrial protein content and enzyme activity (~20-200%). Lean body mass increased (1%; P < 0.01) and fat mass decreased (3%; P < 0.01). No significant effects on fasting blood glucose, insulin, lipids or markers of immune function were observed. There were no significant interactions between drink conditions for training adaptation or blood measurements. For body composition, the Oat/Potato and carbohydrate group decreased leg fat mass significantly more than the Milk group (interaction P < 0.05). Conclusions: Aerobic capacity and body composition were improved and a number of mitochondrial, glycolytic and oxidative skeletal muscle proteins and enzyme activities were upregulated by a 6 week training intervention. However, none of the parameters for endurance training adaptation were influenced by protein supplementation before and after each training session., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Pettersson, Edin, Hjelte, Scheinost, Wagner, Ekblom, Jessen, Madsen and Andersson-Hall.)

Background: Epidemiological associations between maternal concentrations of perfluoroalkyl substances (PFAS) and birth weight are inconsistent. There is concern that studies based on samples collected in late pregnancy may be confounded by kidney function but studies of the relation between pregnancy-induced changes in PFAS and kidney function are lacking. Our aims were to investigate changes in serum concentrations of perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) from early to late pregnancy and to explore relations to changes in glomerular filtration rate (GFR) and glomerular pore size., Methods: We conducted the study in a cohort of 73 pregnancies of normal-weight Swedish women without gestational diabetes and preeclampsia, enrolled 2009-2014. Blood was collected in median weeks 11 and 36, respectively, and analysed PFAS using liquid chromatography-tandem-mass-spectrometry. We estimated GFR based on creatinine and cystatin C and used the ratio eGFR cystatin C /eGFR creatinine to indicate glomerular pore size. We used Wilcoxon signed-rank test to compare early and late measures and partial Spearman rank correlations to explore relations between changes in PFAS and kidney function., Results: Median concentrations of PFNA, PFOA and PFOS decreased by 15-21% but changes were uncorrelated to changes in kidney function (partial R = - 0.06-0.11). The observed increase in median PFHxS concentration of 69% was likely an artefact of systematic measurement error caused by coeluting endogenous inferences., Conclusions: Serum concentrations of PFNA, PFOA and PFOS decrease during pregnancy but the magnitudes of change are unrelated to parallel changes in eGFR and glomerular pore size, suggesting that changes in these indicators of kidney function are not important confounders in studies of PFAS and birth weight in pregnancies without gestational diabetes and preeclampsia.

The Pregnancy Obesity Nutrition and Child Health study is a longitudinal study of reproductive health. Here we analyzed body composition of normal-weight and obese Swedish women by three methods during each trimester of pregnancy. Cross-sectional and longitudinal fat mass estimates using quantitative magnetic resonance (QMR) and bioelectrical impedance analysis (BIA) (Tanita MC-180MA-III) were compared with fat mass determined by air displacement plethysmography (ADP) in pregnancy weeks 8-12, 24-26, and 35-37 in normal-weight women (n = 122, BMI = 22.1 ± 1.6 kg/m 2 ) and obese women (n = 29, BMI = 34.6 ± 3.6 kg/m 2 ). ADP results were calculated from pregnancy-adjusted fat-free mass densities. Mean fat mass by QMR and ADP were similar in obese women, although with wide limits of agreement. In normal-weight women, QMR overestimated mean fat mass in all trimesters, with systematic overestimation at low fat mass values in trimesters 1 and 3. In obese women, fat mass by BIA was grossly underestimated and imprecise in all trimesters, especially at higher values in trimester 2. In normal-weight women, fat mass by BIA was moderately lower than by ADP in trimester 1, similar in trimester 2, and moderately higher in trimester 3. QMR and ADP assessed fat mass changes similarly in obese women, whereas BIA overestimated fat mass changes in normal-weight women. Mean fat mass and fat mass changes by QMR and pregnancy-adjusted ADP were similar in pregnant obese women. Mean fat mass by QMR and fat mass changes by BIA were higher than corresponding values determined by pregnancy-adjusted ADP in normal-weight women.

The purpose of this study was to evaluate the substrate oxidation of three commercially available, 14%-carbohydrate sports drinks with different compositions, osmolality, and pH for their impact on dental exposure to low pH. In a cross-over, randomized double-blinded design, 12 endurance athletes (age 31. 2 ± 7.7 years, V ˙ O 2max 65.6 ± 5.0 mL·kg -1 ) completed 180 min of cycling at 55% W max . During the first 100 min of cycling, athletes consumed amylopectin starch (AP), maltodextrin+sucrose (MD+SUC), or maltodextrin+fructose hydrogel (MD+FRU) drinks providing 95 g carbohydrate·h -1 , followed by water intake only at 120 and 160 min. Fuel use was determined using indirect calorimetry and stable-isotope techniques. Additionally, dental biofilm pH was measured using the microtouch method in a subsample of participants ( n = 6) during resting conditions before, and at different time intervals up to 45 min following a single bolus of drink. Exogenous carbohydrate oxidation (CHO EXO ) during the 2nd hour of exercise was significantly ( P < 0.05) different between all three drinks: MD+FRU (1.17 ± 0.17 g·min -1 ), MD+SUC (1.01 ± 0.13 g·min -1 ), and AP (0.84 ± 0.11 g·min -1 ). At the end of exercise, CHO EXO and blood glucose concentrations (3.54 ± 0.50, 4.07 ± 0.67, and 4.28 ± 0.47 mmol·L -1 , respectively) were significantly lower post MD+FRU consumption than post MD+SUC and AP consumption ( P < 0.05). Biofilm acidogenicity at rest demonstrated a less pronounced pH fall for MD+FRU compared to the acidulant-containing MD+SUC and AP ( P < 0.05). In conclusion, while total intake of MD+FRU showed signs of completed uptake before end of monitoring, this was less so for MD+SUC, and not at all the case for AP. Thus, this study showed that despite carbohydrates being encapsulated in a hydrogel, a higher CHO EXO was observed following MD+FRU drink ingestion compared to AP and MD+SUC consumption upon exposure to the acidic environment of the stomach. This finding may be related to the higher fructose content of the MD+FRU drink compared with the MD+SUC and AP drinks. Furthermore, a carbohydrate solution without added acidulants, which are commonly included in commercial sport drinks, may have less deleterious effects on oral health., (Copyright © 2020 Pettersson, Ahnoff, Edin, Lingström, Simark Mattsson and Andersson-Hall.)

Objective: Detailed data on adipokines and body composition during and after pregnancy in women of different BMI categories are lacking. Furthermore, adipokine regulation during pregnancy and the factors contributing to gestational insulin resistance are not completely understood. The objective was to longitudinally determine adipokine levels, body composition, and insulin sensitivity during and after pregnancy in women of healthy weight (HW) and with obesity (OB), and identify factors associated with insulin resistance., Design: Women (30 HW, 19 OB) underwent blood sampling and body composition examination, by air-displacement plethysmography, longitudinally during pregnancy (trimesters 1, 2, 3) and after pregnancy (6, 12, 18 months postpartum). Serum leptin, soluble leptin receptor (sOB-R), and adiponectin levels were measured and free leptin index (FLI) and homeostatic model assessment of insulin resistance (HOMA-IR) determined., Results: Fat mass and leptin increased during pregnancy in the HW (p < 0.01) but not in the OB group. sOB-R increased during pregnancy in both groups (p < 0.001). Thus, FLI was unchanged in HW throughout pregnancy but reduced in OB (p = 0.001), although consistently higher in OB. Adiponectin decreased in both groups during pregnancy (p < 0.001 for HW, p = 0.01 for OB). After pregnancy, adiponectin increased in both groups, but more markedly in OB where it reached trimester 1 levels. Multivariable regression identified FLI as the variable most strongly associated with HOMA-IR in all trimesters, but not after pregnancy., Conclusions: Leptin, sOB-R, adiponectin, and FLI undergo marked changes during and after pregnancy with differences in women of different BMI. We suggest that leptin activity is regulated by its soluble receptor and that this is an important factor for optimizing fat mass and insulin sensitivity during pregnancy.

Aim: To investigate the degree by which epigenetic signatures in children from mothers with gestational diabetes mellitus (GDM) are influenced by environmental factors. Methods: We profiled the DNA methylation signature of blood from lean, obese and GDM mothers and their respective newborns. Results: DNA methylation profiles of mothers showed high similarity across groups, while newborns from GDM mothers showed a marked distinct epigenetic profile compared with newborns of both lean and obese mothers. Analysis of variance in DNA methylation levels between newborns showed higher variance in the GDM group. Conclusion: Our results suggest that environmental factors, rather than direct transmission of epigenetic marks from the mother, are involved in establishing the epigenetic signature associated with GDM.

Women with previously diagnosed gestational diabetes mellitus (GDM) are at increased risk of type-2-diabetes mellitus (T2D). We aimed to establish links between glucose tolerance (GT) and serum fatty acid (FA) profile in the transition from GDM to T2D. Six years after GDM, 221 women were grouped as having normal GT (NGT), impaired GT (IGT), or T2D based on oral GT test results. Fasting serum FAs were profiled, anthropometric measures taken, and dietary intake determined. Linoleic acid (LA) was significantly higher in NGT women ( p < 0.001) compared with IGT and T2D, and emerged as a strong predictor of low glucose and insulin levels, independently of BMI. Self-reported vegetable oil consumption correlated with LA serum levels and glucose levels. Delta-6-, delta-9-, and stearoyl-CoA-desaturase activities were associated with decreased GT, and delta-5-desaturase activities with increased GT. In a subgroup of women at high risk of diabetes, low LA and high palmitic acid levels were seen in those that developed T2D, with no differences in other FAs or metabolic measurements. Results suggest that proportions of LA and palmitic acid are of particular interest in the transition from GDM to T2D. Interconversions between individual FAs regulated by desaturases appear to be relevant to glucose metabolism.

Aim: Determine the metabolic profile and identify risk factors of women transitioning from gestational diabetes mellitus (GDM) to type 2 diabetes mellitus (T2DM)., Methods: 237 women diagnosed with GDM underwent an oral glucose tolerance test (OGTT), anthropometrics assessment, and completed lifestyle questionnaires six years after pregnancy. Blood was analysed for clinical variables (e.g., insulin, glucose, HbA1c, adiponectin, leptin, and lipid levels) and NMR metabolomics. Based on the OGTT, women were divided into three groups: normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM., Results: Six years after GDM, 19% of subjects had T2DM and 19% IGT. After BMI adjustment, the IGT group had lower HDL, higher leptin, and higher free fatty acid (FFA) levels, and the T2DM group higher triglyceride, FFA, and C-reactive protein levels than the NGT group. IGT and T2DM groups reported lower physical activity. NMR measurements revealed that levels of branched-chain amino acids (BCAAs) and the valine metabolite 3-hydroxyisobyturate were higher in T2DM and IGT groups and correlated with measures of insulin resistance and lipid metabolism., Conclusion: In addition to well-known clinical risk factors, BCAAs and 3-hydroxyisobyturate are potential markers to be evaluated as predictors of metabolic risk after pregnancy complicated by GDM.

Objective: To study changes of neuropeptides and adipokines in cerebrospinal fluid (CSF) and serum from pregnancy to postpregnancy in relation to weight changes, fat mass and glucose metabolism., Context: With high postpartum weight retention being a risk factor in future pregnancies and of lifelong obesity, we evaluated neuropeptide and adipokine changes in women who either gained weight or were weight stable., Design: Women were followed for 5 ± 1 years after pregnancy and divided into two groups, weight stable and weight gain, by weight change from start of pregnancy., Patients: Twenty-five women (BMI 27 ± 5 kg/m 2 ) recruited at admission for elective caesarean section., Measurements: CSF and serum levels of agouti-related protein (AgRP), leptin and insulin, and serum levels of adiponectin and soluble leptin receptor were measured during and after pregnancy. These measurements were further related to fat mass and insulin sensitivity (HOMA-IR)., Results: S-AgRP levels during pregnancy were lower in the weight stable group and a 1 unit increase in s-AgRP was associated with 24% higher odds of pertaining to the weight gain group. After pregnancy, s-AgRP increased in the weight stable group but decreased in the weight gain group. Decreased transport of leptin into CSF during pregnancy was reversed by an increased CSF:serum leptin ratio after pregnancy. In women who returned to their prepregnancy weight, serum adiponectin increased after pregnancy and correlated negatively with HOMA-IR., Conclusion: S-AgRP concentration in late pregnancy may be one factor predicting weight change after pregnancy, and circulating AgRP may be physiologically important in the long-term regulation of body weight., (© 2017 John Wiley & Sons Ltd.)

Purpose: This study investigated how postexercise intake of placebo (PLA), protein (PRO), or carbohydrate (CHO) affected fat oxidation (FO) and metabolic parameters during recovery and subsequent exercise., Methods: In a cross-over design, 12 moderately trained women (VO 2max 45 ± 6 ml·min -1 ·kg -1 ) performed three days of testing. A 23-min control (CON) incremental FO bike test (30-80% VO 2max ) was followed by 60 min exercise at 75% VO 2max . Immediately postexercise, subjects ingested PLA, 20 g PRO, or 40 g CHO followed by a second FO bike test 2 h later., Results: Maximal fat oxidation (MFO) and the intensity at which MFO occurs (Fat max ) increased at the second FO test compared to the first following all three postexercise drinks (MFO for CON = 0.28 ± 0.08, PLA = 0.57 ± 0.13, PRO = 0.52 ± 0.08, CHO = 0.44 ± 0.12 g fat·min -1 ; Fat max for CON = 41 ± 7, PLA = 54 ± 4, PRO = 55 ± 6, CHO = 50 ± 8 %VO 2max , p < 0.01 for all values compared to CON). Resting FO, MFO, and Fat max were not significantly different between PLA and PRO, but lower for CHO. PRO and CHO increased insulin levels at 1 h postexercise, though both glucose and insulin were equal with PLA at 2 h postexercise. Increased postexercise ketone levels only occurred with PLA., Conclusion: Protein supplementation immediately postexercise did not affect the doubling in whole body fat oxidation seen during a subsequent exercise trial 2 h later. Neither did it affect resting fat oxidation during the postexercise period despite increased insulin levels and attenuated ketosis. Carbohydrate intake dampened the increase in fat oxidation during the second test, though a significant increase was still observed compared to the first test.

Factors differentiating women at highest risk of progression to type 2 diabetes mellitus (T2DM) after gestational diabetes mellitus (GDM) are incompletely known. Our aim was to characterize adipose tissue and body composition in relation to glucose metabolism in women with a history of GDM and to identify factors associated with development of T2DM. We examined glucose tolerance (OGTT), insulin sensitivity (HOMA-IR), body composition (anthropometry, air displacement plethysmography), and blood chemistry in 39 women 6 years after GDM. An adipose tissue biopsy was obtained to assess the size, number, and lipolytic activity of adipocytes, and adipokine release and density of immune cells and blood vessels in adipose tissue. Normal glucose tolerance (NGT) was identified in 31 women and impaired glucose metabolism (IGM) in 8. Women with IGM had higher BMI/fat mass, and related expected adipose tissue features, than women with NGT. Ethnicity was similar in the groups, but numerically there was a higher proportion of European women in the NGT group and a higher proportion of non-European women in the IGM group. BMI was the best discriminator of NGT versus IGM (multivariable logistic regression: OR = 1.34, P < 0.01). Waist-to-height ratio and adipocyte volume were most strongly associated with HOMA-IR (multivariable linear regression: R 2  = 0.656, P < 0.001). After adjustment for BMI/ethnicity, women with IGM had increased serum adipocyte fatty acid-binding protein, weight gain after index pregnancy, and a lower proportion of fat-free mass. These factors, together with high BMI, abdominal fat distribution, and enlarged adipocytes, may increase the risk of progression to T2DM after GDM.

Objective: During pregnancy, metabolic interactions must be adapted, though neuroendocrine mechanisms for increased food intake are poorly understood. The objective of this study was to characterize differences in insulin, leptin, and agouti-related protein (AgRP) levels in serum and cerebrospinal fluid (CSF) in pregnant women with normal weight (NW) and pregnant women with overweight (OW) or obesity (OB). Placenta as a source for increased peripheral AgRP levels during pregnancy was also investigated., Methods: Women were recruited at admission for elective cesarean section. Insulin, AgRP, and leptin were measured in serum and CSF from 30 NW, 25 OW, and 21 OB at term. Serum during pregnancy and placenta at term were collected for further AgRP analysis., Results: Immunohistology showed placental production of AgRP and serum AgRP levels increased throughout pregnancy. CSF AgRP, leptin, and insulin levels were higher in OW and OB than NW. Serum leptin and insulin levels were higher and AgRP lower in OB than NW., Conclusions: High serum AgRP levels might protect from the suppressive effects of leptin during pregnancy. Pregnant women with OB and OW might further be protected from the suppressive effect of leptin by high CSF AgRP levels. Evidence was found, for the first time, of human placental AgRP production mirrored by levels in the circulation., (© 2016 The Obesity Society.)

The purpose of this study was to compare whole-body fat oxidation kinetics after prior exercise with overnight fasting in elite endurance athletes. Thirteen highly trained athletes (9 men and 4 women; maximal oxygen uptake: 66 ± 1 mL·min(-1)·kg(-1)) performed 3 identical submaximal incremental tests on a cycle ergometer using a cross-over design. A control test (CON) was performed 3 h after a standardized breakfast, a fasting test (FAST) 12 h after a standardized evening meal, and a postexercise test (EXER) after standardized breakfast, endurance exercise, and 2 h fasting recovery. The test consisted of 3 min each at 30%, 40%, 50%, 60%, 70%, and 80% of maximal oxygen uptake and fat oxidation rates were measured through indirect calorimetry. During CON, maximal fat oxidation rate was 0.51 ± 0.04 g·min(-1) compared with 0.69 ± 0.04 g·min(-1) in FAST (P < 0.01), and 0.89 ± 0.05 g·min(-1) in EXER (P < 0.01). Across all intensities, EXER was significantly higher than FAST and FAST was higher than CON (P < 0.01). Blood insulin levels were lower and free fatty acid and cortisol levels were higher at the start of EXER compared with CON and FAST (P < 0.05). Plasma nuclear magnetic resonance-metabolomics showed similar changes in both EXER and FAST, including increased levels of fatty acids and succinate. In conclusion, prior exercise significantly increases whole-body fat oxidation during submaximal exercise compared with overnight fasting. Already high rates of maximal fat oxidation in elite endurance athletes were increased by approximately 75% after prior exercise and fasting recovery.

Despite recent advances in imaging diagnostic technology and additional treatment options our ability to prevent or inhibit discogenic back pain has not drastically improved. The challenge of linking early degenerative patterns to dysfunction and pain remains. Using a novel material testing device designated the tissue diagnostic instrument (TDI) we measured the local stiffness and strain energy absorption in the radial direction of 13 intact intervertebral discs; effectively generating a mechanical profile of each disc. Prior to measuring mechanical properties, an MR image was taken of each spine segment and the discs were radiologically scored according to the Pfirrmann scale. After testing, a sagittal portion of each L1-L2 disc was excised from each of four spines for histology. No significant correlations were found between Pfirrmann grade and mechanical data. However, polarized light microscopy images of disc sections indicated correlations between local tissue modulus measured with the TDI and the clarity and density of lamellar striations.

This study examined the effect of ethnic group membership on ethnic identity, race-related stress, and quality of life (QOL). The Multigroup Ethnic Identity Measure, the Index of Race Related Stress--Brief Version, and the World Health Organization Quality of Life--Brief Version were administered to 160 male and female participants from 3 ethnic groups (African American, Asian American, and Latino American). Results indicated that African American participants had significantly higher race-related stress, ethnic identity, and psychological QOL scores than did Asian and Latino American participants. A stepwise multiple regression analysis revealed that ethnic identity and cultural racism were significant predictors of QOL and accounted for 16% of the total variance for the entire sample.

This study compared porcelain facial margins made with the direct-lift technique using high-fusing shoulder porcelains and the platinum foil technique with conventional body porcelain. Marginal accuracy was measured directly and the marginal sharpness computed by the software program MacDraft. Both Vita high-fusing shoulder porcelain and Vita SM 90 porcelain produced restorations that had significantly smaller mean facial marginal openings than crowns created with platinum foil. However, the SM 90 porcelain recorded significantly greater cross sectional or internal marginal discrepancies than the other two techniques (p < 0.05). Externally, the shoulder porcelains followed the facial rounding of the stone die; thus porcelain marginal roundings can be manifested as either negative roundings or underextensions and positive roundings or overextensions. The lack of marginal sharpness of porcelain facial margins may be influenced more by the die material rather than by the marginal porcelain or the technique.

The sleep-waking behavior of a male infant, normal with respect to pregnancy, delivery and Apgar score, was observed continuously from birth till the first 4 months of life. The infant was allowed to sleep and awake according to his own schedule and was fed only if his behavior could be judged as a feeding demand. Using several methods of computerized analysis it could be demonstrated that the spontaneous sleep-waking behavior was mainly driven by two endogenous rhythms, an ultradian cycle and a circadian one. While the ultradian rhythm was already established at term showing a mean period of 4 h, the circadian variation developed during the first 3 months of life. So far our results support earlier studies (KLEITMAN and ENGELMANN; PARMELEE; HELLBRUGGE,). The present paper, however, gives further evidence that both rhythms do not run independently, but seem to constitute a system of connected oscillators. As soon as the circadian rhythm is manifestly developed, the period of the ultradian rhythm seems to be modulated according to circadian variations. More specifically, during the nocturnal phase of the circadian rhythm the ultradian rhythm decelerated. By contrast, during the diurnal phase the ultradian cycle was accelerated. Using circadian frequency modulation of the ultradian cycle as the underlying principle, a computerized model of both connected oscillators was developed. The theoretically predicted sleep-waking behavior was compared to the behavior actually observed in the infant of this study. During postnatal development the coupled rhythms cause characteristic periodicities of the sleep-waking pattern. Since the infant experiences his world within a basic framework of sleep and waking spans, the different periodicities may be considered as a structure timing the information process in the developing brain.

The spontaneous sleep-waking behaviour of a male infant, normal with respect to pregnancy, delivery and Apgar score, was observed continuously from birth till the first four months of life. Additionally sleep stages were scored by means of polygraphic method during several weeks. The infant was allowed to sleep and awake according to his own schedule and was fed if his behaviour could be judged as a feeding demand. Using statistical analysis it could be deomonstrated, that the spontaneous sleep-waking behaviour was mainly driven by three endogenous rhythms: The Basic rest aktivity cycle with periods of about 50 minutes, a circafour-hour rhythm already established at term and a circadian periodicity which developed during the first three months of life. So far our results support earlier studies of Kleitman and Engelmann, Parmelee, Hellbrügge etc. The present study, however, gives further evidence, that these rhythms do not run independently, but constitute a system of interacting oscillators. During postnatal development these connected rhythms cause characteristic periodicities of the spontaneous sleep-waking pattern. Since the newborn experiences his world within a basic framework of sleep and waking epochs, the system of interacting, endogenous rhythms may be considered as a structure timing the information process in the developing brain.