Interaction of Iron Homeostasis and Fatty Acid Metabolism in the Development of Glucose Intolerance in Women with Previous Gestational Diabetes Mellitus.

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.

Validation of Oura ring energy expenditure and steps in laboratory and free-living.

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.

Exercise, aerobic fitness, and muscle strength in relation to glucose tolerance 6 to 10 years after gestational diabetes.

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 (VO2peak), 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). VO2peak and muscle strength were lowest in the T2D group. In a regression analysis, VO2peak 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 VO2peak 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.

Physical activity during pregnancy and association with changes in fat mass and adipokines in women of normal-weight or with obesity.

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.

Growth differentiation factor 15 increases in both cerebrospinal fluid and serum during pregnancy.

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.

High levels of serum vitamin D-binding protein in patients with psoriasis: A case-control study and effects of ultraviolet B phototherapy.

The role of vitamin D in psoriasis remains contradictory despite the fact that vitamin D analogues constitute an established treatment for psoriasis. It has been proposed that the ability of vitamin D to exert anti-inflammatory effects might not depend solely on the concentration of serum 25(OH)D but also on the concentration of vitamin D-binding protein (DBP). High concentrations of DBP might diminish vitamin D's biologic action. The aims of this study were (i) to analyze the serum levels of DBP, total and calculated free 25(OH)D in patients with psoriasis and compare the results with healthy controls and (ii) to study the effect of ultraviolet B (UVB) phototherapy on DBP levels. Caucasian subjects (n = 68) with active plaque psoriasis were compared with a population-based sample of men and women (n = 105), matched for age and sex. Season of enrollment was taken into consideration. The patients were also studied before and after UVB phototherapy. The severity of the disease was calculated as Psoriasis Area Severity Index (PASI). DBP, free 25(OH)D index and total 25(OH)D were higher in patients with psoriasis compared with controls (P= 0.004, P = 0.045 and P < 0.0001, respectively). DBP did not change after phototherapy, whereas 25(OH)D increased and intact parathyroid hormone (iPTH) decreased (P < 0.001 for both). Psoriasis improved and PASI decreased after phototherapy (P < 0.001). There was no correlation between DBP and 25(OH)D or between DBP and PASI. Measurement of DBP is recommended when evaluating vitamin D status in patients with psoriasis. High DBP levels in psoriasis imply a disturbed vitamin D pathway that warrants further investigation. Direct measurement of free 25(OH)D, instead of total 25(OH)D that circumvents abnormally high levels of DBP, could be considered.

Growth-differentiation-factor 15 levels in obese and healthy pregnancies: Relation to insulin resistance and insulin secretory function.

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.

Infant body composition relationship to maternal adipokines and fat mass: the PONCH study.

BACKGROUND: Infant adiposity is linked to both high maternal fat mass (FM) and excessive gestational FM gain, whereas the association with maternal adipokines is less clear. The aim was to determine how levels of maternal leptin, the soluble leptin receptor (sOB-R), adiponectin, and FM during pregnancy were linked to infant FM in normal-weight (NW) women and women with obesity (OB). METHODS: Body composition and serum levels of leptin, adiponectin, and sOB-R were determined three times during pregnancy in 80 NW and 46 OB women. For infants, body composition was measured at 1 and 12 weeks of age. RESULTS: Maternal leptin and sOB-R levels increased during pregnancy. For NW women, infant FM at 1 week was inversely associated with changes in maternal leptin and at 12 weeks inversely associated with absolute maternal sOB-R levels throughout pregnancy, as well as changes in sOB-R levels in early pregnancy. For OB women, infant FM at both 1 and 12 weeks were best explained by maternal FM. CONCLUSIONS: Leptin and sOB-R, thought to regulate leptin bioavailability, are associated with fat accumulation in infants born to NW women. In OB women, maternal FM in early pregnancy is more important than leptin in determining infant fat accumulation. IMPACT: In normal-weight women, the regulation of maternal leptin bioavailability during pregnancy has a role in infant fat mass accumulation. In women with obesity, however, pre-pregnancy maternal fat mass seems more important for infant fat mass. This is the first study of maternal adipokines and fat mass including longitudinal measurements in both mothers and their children. Understanding the relationship between maternal factors and infant fat mass is of great importance as obesity is programmed over the generations, and it is important to learn what regulates this programming.

Pregnancy-induced changes in serum concentrations of perfluoroalkyl substances and the influence of kidney function.

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 eGFRcystatin C/eGFRcreatinine 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.

Body Composition During Pregnancy: Longitudinal Changes and Method Comparisons.

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/m2) and obese women (n = 29, BMI = 34.6 ± 3.6 kg/m2). 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.

Longitudinal changes in adipokines and free leptin index during and after pregnancy in women with obesity.

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.

Environmental factors influence the epigenetic signature of newborns from mothers with gestational diabetes.

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.

Maternal obesity and gestational diabetes mellitus affect body composition through infancy: the PONCH study.

BACKGROUND: To determine how maternal obesity or gestational diabetes mellitus (GDM) affect infant body size and body composition during the first year of life. METHODS: Eighty three normal-weight (NW) women, 26 obese (OB) women, and 26 women with GDM were recruited during pregnancy. Infant body composition was determined by air-displacement plethysmography at 1 and 12 weeks, and anthropometric measurements made until 1 year of age. RESULTS: Girl infants born to OB women and women with GDM had a higher body-fat percentage (BF%) at 1 and 12 weeks of age than girls born to NW women. Girls had higher BF% than boys in OB and GDM groups only. Maternal HbA1c and fasting plasma glucose correlated with girl infant BF% at 1 week of age. Maternal weight at start of pregnancy correlated with birthweight in NW and OB groups, but not the GDM group. OB group infants showed greater BMI increases from 1 week to 1 year than both NW and GDM group infants. CONCLUSION: Results show that both maternal glycaemia and obesity are determinants of increased early life adiposity, especially in girls, with glycaemic levels being more influential than maternal weight for infants born to women with GDM.

Circulating Linoleic Acid is Associated with Improved Glucose Tolerance in Women after Gestational Diabetes.

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.

Adipose tissue and body composition in women six years after gestational diabetes: factors associated with development of type 2 diabetes.

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: R2 = 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.

Higher Concentrations of BCAAs and 3-HIB Are Associated with Insulin Resistance in the Transition from Gestational Diabetes to Type 2 Diabetes.

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.

Free lipid and computerized determination of adipocyte size.

The size distribution of adipocytes in a suspension, after collagenase digestion of adipose tissue, can be determined by computerized image analysis. Free lipid, forming droplets, in such suspensions implicates a bias since droplets present in the images may be identified as adipocytes. This problem is not always adjusted for and some reports state that distinguishing droplets and cells is a considerable problem. In addition, if the droplets originate mainly from rupture of large adipocytes, as often described, this will also bias size analysis. We here confirm that our ordinary manual means of distinguishing droplets and adipocytes in the images ensure correct and rapid identification before exclusion of the droplets. Further, in our suspensions, prepared with focus on gentle handling of tissue and cells, we find no association between the amount of free lipid and mean adipocyte size or proportion of large adipocytes.

Central and peripheral leptin and agouti-related protein during and after pregnancy in relation to weight change.

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/m2 ) 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.

Pregnancy to postpartum transition of serum metabolites in women with gestational diabetes.

CONTEXT: Gestational diabetes is commonly linked to development of type 2 diabetes mellitus (T2DM). There is a need to characterize metabolic changes associated with gestational diabetes in order to find novel biomarkers for T2DM. OBJECTIVE: To find potential pathophysiological mechanisms and markers for progression from gestational diabetes mellitus to T2DM by studying the metabolic transition from pregnancy to postpartum. DESIGN: The metabolic transition profile from pregnancy to postpartum was characterized in 56 women by mass spectrometry-based metabolomics; 11 women had gestational diabetes mellitus, 24 had normal glucose tolerance, and 21 were normoglycaemic but at increased risk for gestational diabetes mellitus. Fasting serum samples collected during trimester 3 (gestational week 32±0.6) and postpartum (10.5±0.4months) were compared in diagnosis-specific multivariate models (orthogonal partial least squares analysis). Clinical measurements (e.g., insulin, glucose, lipid levels) were compared and models of insulin sensitivity and resistance were calculated for the same time period. RESULTS: Women with gestational diabetes had significantly increased postpartum levels of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine, and their circulating lipids did not return to normal levels after pregnancy. The increase in BCAAs occurred postpartum since the BCAAs did not differ during pregnancy, as compared to normoglycemic women. CONCLUSIONS: Postpartum levels of specific BCAAs, notably valine, are related to gestational diabetes during pregnancy.