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OBJECTIVE High cereal fiber and low-glycemic index (GI) diets are associated with reduced cardiovascular disease (CVD) risk in cohort studies. Clinical trial evidence on event incidence is lacking. Therefore, to make trial outcomes more directly relevant to CVD, we compared the effect on carotid plaque development in diabetes of a low-GI diet versus a whole-grain wheat-fiber diet. RESEARCH DESIGN AND METHODS The study randomized 169 men and women with well-controlled type 2 diabetes to counseling on a low GI-diet or whole-grain wheat-fiber diet for 3 years. Change in carotid vessel wall volume (VWV) (prespecified primary end point) was assessed by MRI as an indication of arterial damage. RESULTS Of 169 randomized participants, 134 completed the study. No treatment differences were seen in VWV. However, on the whole-grain wheat-fiber diet, VWV increased significantly from baseline, 23 mm3 (95% CI 4, 41; P = 0.016), but not on the low-GI diet, 8 mm3 (95% CI −10, 26; P = 0.381). The low-GI diet resulted in preservation of renal function, as estimated glomerular filtration rate, compared with the reduction following the wheat-fiber diet. HbA1c was modestly reduced over the first 9 months in the intention-to-treat analysis and extended with greater compliance to 15 months in the per-protocol analysis. CONCLUSIONS Since the low-GI diet was similar to the whole-grain wheat-fiber diet recommended for cardiovascular risk reduction, the low-GI diet may also be effective for CVD risk reduction.

Objective: To compare postpartum glucose tolerance between women treated for gestational diabetes (GDM) and those not treated. Methods: Metabolic testing was performed at 3-months and 1-year postpartum in 599 women comprising the following gestational glucose tolerance groups: (I) normal glucose challenge test (GCT) and oral glucose tolerance test (OGTT) in pregnancy; (II) abnormal GCT with normal OGTT; (III) gestational impaired glucose tolerance; (IV) mild untreated GDM; and (V) severe treated GDM. Results: Birthweight progressively increased across Groups I-IV, before falling steeply in treated GDM (p Conclusion: Treating GDM lowers birthweight but does not disrupt the association between gestational glycemia and maternal pre-diabetes/diabetes after pregnancy.

Although kidney transplantation (KT) has been shown to ameliorate adverse left ventricular (LV) remodelling associated with end stage kidney disease, its effects on the right ventricle have not been well studied. Recently, strain imaging has been shown to be a sensitive measure of early subclinical myocardial dysfunction. Using cardiac magnetic resonance imaging (MRI), we examined the effects of KT on right ventricular (RV) strain parameters. In a cohort of 81 patients (39 patients underwent KT and 42 patients remained on dialysis as control group), cardiac MRI studies were obtained at baseline and at 1 year follow-up. There were no significant differences in RV strain values between the groups at baseline. After 1 year, RV strain values did not significantly change in patients who received KT, and changes in RV strain over 1 year were not significantly different between the KT and the dialysis groups. Given the previously demonstrated improvement in LV strain post-KT, the current study suggests that RV and LV remodelling post-KT may have different mechanisms. Further studies elucidating the effects of KT on RV remodelling are needed.

OBJECTIVETo compare postpartum glucose tolerance between women treated for gestational diabetes mellitus (GDM) and those not treated.RESEARCH DESIGN AND METHODSMetabolic testing was performed at 3 and 12 months postpartum in 599 women comprising the following gestational glucose tolerance groups: 1) normal glucose challenge test (GCT) and oral glucose tolerance test (OGTT) during pregnancy, 2) abnormal GCT with normal OGTT, 3) gestational impaired glucose tolerance, 4) mild untreated GDM, and 5) severe treated GDM.RESULTSBirth weight progressively increased across groups 1–4 before falling steeply in treated GDM (P < 0.0001). In contrast, at 3 and 12 months, insulin sensitivity and β-cell function progressively decreased across the five groups, mirrored by rising fasting and 2-h glucose (all P < 0.0001). Accordingly, prevalence of prediabetes/diabetes at 12 months increased in a stepwise manner across groups 1–5 (2.8%, 9.6%, 13.5%, 21.5%, and 32.6%, respectively; P < 0.0001).CONCLUSIONSTreating GDM lowers birth weight but does not disrupt the association between gestational glycemia and maternal prediabetes/diabetes after pregnancy.

OBJECTIVE To determine the association of adipose tissue insulin resistance with longitudinal changes in biomarkers of adipose tissue function, circulating lipids, and dysglycemia. RESEARCH DESIGN AND METHODS Adults at risk for type 2 diabetes in the Prospective Metabolism and Islet Cell Evaluation (PROMISE) cohort had up to four assessments over 9 years (n = 468). Adipose tissue insulin resistance was determined using a novel validated index, Adipo-IR, calculated as the product of fasting insulin and nonesterified fatty acids measured at baseline. Fasting serum was used to measure biomarkers of adipose tissue function (adiponectin and soluble CD163 [sCD163]), circulating lipids (total cholesterol, HDL, LDL, triglyceride [TG]), and systemic inflammation (interleukin-6 [IL-6] and tumor necrosis factor-α [TNF-α]). Incident dysglycemia was defined as the onset of impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes at follow-up. Generalized estimating equation (GEE) models were used to assess the relationship of Adipo-IR with longitudinal outcomes. RESULTS GEE analyses showed that elevated Adipo-IR was longitudinally associated with adipose tissue dysfunction (adiponectin −4.20% [95% CI −6.40 to −1.95]; sCD163 4.36% [1.73–7.06], HDL −3.87% [−5.15 to −2.57], TG 9.26% [5.01–13.69]). Adipo-IR was associated with increased risk of incident dysglycemia (odds ratio 1.59 [95% CI 1.09–2.31] per SD increase). Associations remained significant after adjustment for waist circumference and surrogate indices for insulin resistance. There were no significant longitudinal associations of Adipo-IR with IL-6, TNF-α, total cholesterol, or LDL. CONCLUSIONS Our findings demonstrate that adipose tissue insulin resistance is prospectively associated with adipose tissue function, HDL, TG, and incident dysglycemia.

Worsening renal function in chronic kidney disease correlates with worsening right ventricular (RV) systolic function. We evaluated the association between kidney transplantation (KT) and RV structure and systolic function, and the relationships between RV and left ventricular (LV) changes, blood pressure, and specific cardiac biomarkers, in patients with end-stage kidney disease using cardiac magnetic resonance imaging (CMR). In this prospective, multi-centre, cohort study, 39 adult patients on dialysis receiving KT and 42 patients eligible for, but not yet receiving KT, were recruited. CMR was performed at baseline, and repeated at 12 months. Among 81 patients (mean age 51 years, 30% female), RV end-diastolic volume index (RVEDVi), end-systolic volume index (RVESVi), mass index (RVMi), and ejection fraction (RVEF) did not change significantly within either the dialysis or KT group over 12 months (all p ≥ 0.10). There were no significant differences in the 12-month changes of these parameters between the dialysis and KT groups (all p ≥ 0.10). RVMI demonstrated positive correlations with NT-proBNP and systolic blood pressure, but not GDF-15, at baseline and at 12 months. Changes in RVEDVi, RVESVi, and RVEF were positively correlated with changes in LVEDVi, LVESVi, and LVEF, respectively over 12 months (Spearman r = 0.72, 0.52, and 0.41; all p

OBJECTIVE The continuum of maternal glycemia in pregnancy shows continuous associations with both 1) neonatal birth weight at delivery and 2) subsequent adiposity later in childhood. While treating gestational diabetes mellitus (GDM) can lower birth weight and thereby disrupt the former association, it is unclear if such treatment reduces childhood adiposity. Thus, we sought to compare anthropometry across the 1st year of life between infants born to women who were treated for GDM and those with lesser degrees of gestational dysglycemia (untreated). RESEARCH DESIGN AND METHODS Anthropometric measurements were performed at 3 months and 12 months of life in 567 infants born to women comprising the following four gestational glucose tolerance groups: 1) women with normoglycemia on both glucose challenge test (GCT) and oral glucose tolerance test (OGTT) in pregnancy; 2) women with an abnormal GCT but normal OGTT; 3) those with mild gestational impaired glucose tolerance; and 4) women treated for GDM. RESULTS Birth weight progressively increased across the three untreated groups but was lowest in women treated for GDM (P = 0.0004). Similarly, women treated for GDM had the lowest rate of macrosomia (P = 0.02). Conversely, however, there were no differences among the four groups in weight z score, length z score, weight-for-length z score, or BMI z score at either 3 months or 12 months (all P values = NS). Similarly, there were no differences among the groups in triceps/biceps/subscapular/suprailiac skinfold thickness or sum of skinfolds at either 3 months or 12 months (all P values = NS). CONCLUSIONS Despite reducing birth weight and macrosomia, the treatment of GDM does not have analogous effects on infant adiposity across the 1st year of life.

Increased left atrial (LA) size predicts cardiovascular events in patients with end-stage kidney disease. There is a paucity of data on LA changes after kidney transplantation (KT). Accordingly, we used cardiac magnetic resonance imaging (CMR) to evaluate LA remodeling after KT, and examined its relationship with left ventricular (LV) measurements, blood pressure and cardiac biomarkers. In this prospective multi-center cohort study, 39 pre-transplant dialysis patients underwent KT and 42 eligible transplant recipients remained on dialysis. CMR, blood pressure and serum measurements for N-terminal pro b-type natriuretic peptide (NT-proBNP), high sensitivity C-reactive protein (hsCRP), and growth differentiation factor-15 (GDF-15) were performed at baseline and 12 months. After 12 months, there were no significant changes in LA end-systolic volume index, LA end-diastolic volume index, or LA ejection fraction (LAEF) within the KT or dialysis group; changes over time did not differ between the 2 groups (all p > 0.25). At baseline and over 12 months, LA volumes and LAEF positively correlated with LV volumes and mass while LAEF positively correlated with LV function. Changes in LA volumes also positively correlated with NT-proBNP and systolic blood pressure (sBP) while LAEF negatively correlated with NT-proBNP. GDF-15 correlated with LA measurements at baseline but not in 12-month changes. hsCRP did not correlate with any LA measurements. LA volumes and function as measured by CMR did not change significantly over 12 months post-KT. There were significant associations between LA and LV remodeling, NT-proBNP and sBP, suggesting common underlying pathophysiological mechanisms.

Objectives Serum markers of iron storage have been linked to type 2 diabetes; however, the mechanism underlying this association is unclear. In pregnancy, increased serum ferritin has been reported in women with gestational diabetes (GDM), a patient population at high risk of future type 2 diabetes. However, in the years after pregnancy, it is not known if ferritin relates to their diabetes risk or the pathophysiologic determinants thereof (insulin sensitivity and beta-cell function). Therefore, we sought to characterize the relationship between ferritin and glucose homeostasis in the early postpartum years in women with and without recent GDM. Methods At both 1 and 3 years postpartum, 340 women (105 with recent GDM) underwent serum ferritin measurement and an oral glucose tolerance test that enabled assessment of insulin sensitivity and/or resistance (Matsuda index and Homeostasis Model Assessment [HOMA-IR]), beta-cell function (Insulin Secretion-Sensitivity Index-2 and insulinogenic index/HOMA-IR) and glucose tolerance. Results Serum ferritin did not differ between women who had GDM and their peers at either 1 or 3 years postpartum. Baseline-adjusted change in ferritin between 1 and 3 years correlated with the concomitant change in C-reactive protein (r=0.21, p=0.0002) but was not associated with measures of insulin sensitivity and/or resistance, beta-cell function or glycemia. On adjusted analyses, neither baseline ferritin nor its change from 1 to 3 years was independently associated with any of the following metabolic outcomes at 3-years postpartum: Matsuda index, HOMA-IR, Insulin Secretion-Sensitivity Index-2, insulinogenic index/HOMA-IR, fasting glucose, 2-h glucose or glucose intolerance. Conclusions Serum ferritin is not associated with glucose homeostasis in the early years after a GDM pregnancy.

Background Recent studies have suggested that gestational diabetes (GDM) is a heterogeneous condition with distinct subtypes determined by whether the predominant metabolic abnormality is impaired insulin sensitivity or deficient insulin secretion. However, it is not known if the elevated future risk of pre-diabetes/diabetes associated with GDM varies according to these subtypes. Thus, we sought to evaluate maternal metabolic function in the 1st year postpartum in relation to GDM subtypes. Methods In this prospective cohort study conducted in Toronto, Canada, 613 women underwent GDM screening by oral glucose tolerance test (OGTT) in pregnancy, followed by repeat OGTT at both 3-months and 12-months postpartum between 09/2003 and 03/2016. The antepartum OGTT identified 3 groups of women: GDM with predominant sensitivity defect (GDM-sensitivity), GDM with predominant secretion defect (GDM-secretion), and non-GDM. Findings Antepartum findings persisted after pregnancy, with lower insulin sensitivity in GDM-sensitivity (Matsuda index; HOMA-IR) and lower insulin secretion in GDM-secretion (Stumvoll first-phase; insulinogenic index (IGI)) at both 3-months and 12-months (all p

ContextSerum uric acid has been linked to risk of type 2 diabetes (T2DM), but debate persists as to whether it plays a causal role. Indeed, it is unclear if changes in uric acid relate to the pathophysiologic determinants of T2DM (insulin resistance, beta-cell dysfunction), as would be expected if causal.ObjectiveTo evaluate the impact of changes in uric acid over 2 years on changes in insulin sensitivity, beta-cell function, and glycemia in women with and without recent gestational diabetes (GDM), a model of the early natural history of T2DM.Design/Setting/ParticipantsAt both 1 and 3 years postpartum, 299 women (96 with recent GDM) underwent uric acid measurement and oral glucose tolerance tests that enabled assessment of insulin sensitivity/resistance (Matsuda index, homeostasis model assessment of insulin resistance [HOMA-IR]), beta-cell function (insulin secretion-sensitivity index-2 [ISSI-2], insulinogenic index/HOMA-IR [IGI/HOMA-IR]), and glucose tolerance.ResultsWomen with recent GDM had higher serum uric acid than their peers at both 1 year (281 ± 69 vs 262 ± 58 µmol/L, P = 0.01) and 3 years postpartum (271 ± 59 vs 256 ± 55 µmol/L, P = 0.03), coupled with lower insulin sensitivity, poorer beta-cell function, and greater glycemia (all P < 0.05). However, on fully adjusted analyses, neither uric acid at 1 year nor its change from 1 to 3 years was independently associated with any of the following metabolic outcomes at 3 years postpartum: Matsuda index, HOMA-IR, ISSI-2, IGI/HOMA-IR, fasting glucose, 2-hour glucose, or glucose intolerance.ConclusionSerum uric acid does not track with changes over time in insulin sensitivity, beta-cell function, or glycemia in women with recent GDM, providing evidence against causality in its association with diabetes.

BACKGROUND Growth differentiation factor 15 (GDF15) is markedly increased in end-stage kidney disease and has been related to increased mortality in patients on dialysis. We hypothesized that kidney transplantation would decrease both GDF15 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and that GDF-15 decrease relates to post-kidney transplantation allograft function. METHODS End-stage kidney disease patients on dialysis awaiting a living donor kidney transplantation (n = 39), and those expected to be on the deceased donor waitlist for at least 12 months (n = 43) were enrolled at three transplant centers. Serum GDF15 and NT-proBNP were measured at 0, 3, and 12 months post-kidney transplantation or post-enrollment. Change in serum GDF15 and NT-proBNP concentrations, and their relation to estimated glomerular filtration rate (eGFR) were assessed by non-parametric tests and regression analyses. RESULTS Median baseline GDF15 was 4744 pg/ml and 5451 pg/ml for the kidney transplantation and dialysis groups, respectively (p = 0.09). Kidney transplantation resulted in a significant decrease in GDF15 (month 12 median 1631 pg/ml, p

Context Chronic inflammation arising from adipose tissue macrophage (ATM) activation may be central in type 2 diabetes etiology. Our objective was to assess the longitudinal associations of soluble CD163 (sCD163), a novel biomarker of ATM activation, with insulin sensitivity, β-cell function, and dysglycemia in high-risk subjects. Methods Adults at risk for type 2 diabetes in the Prospective Metabolism and Islet Cell Evaluation (PROMISE) study had 3 assessments over 6 years (n = 408). Levels of sCD163 were measured using fasting serum. Insulin sensitivity was assessed by HOMA2-%S and the Matsuda index (ISI). β-cell function was determined by insulinogenic index (IGI) over HOMA-IR and insulin secretion-sensitivity index-2 (ISSI-2). Incident dysglycemia was defined as the onset of impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes. Generalized estimating equations (GEE) evaluated longitudinal associations of sCD163 with insulin sensitivity, β-cell function, and incident dysglycemia adjusting for demographic and lifestyle covariates. Areas under receiver-operating-characteristic curve (AROC) tested whether sCD163 improved dysglycemia prediction in a clinical model. Results Longitudinal analyses showed significant inverse associations between sCD163 and insulin sensitivity (% difference per standard deviation increase of sCD163 for HOMA2-%S (β = −7.01; 95% CI, −12.26 to −1.44) and ISI (β = −7.60; 95% CI, −11.09 to −3.97) and β-cell function (ISSI-2 (β = −4.67; 95 %CI, −8.59 to −0.58) and IGI/HOMA-IR (β = −8.75; 95% CI, −15.42 to −1.56)). Increased sCD163 was associated with greater risk for incident dysglycemia (odds ratio = 1.04; 95% CI, 1.02-1.06; P < 0.001). Adding sCD163 data to a model with clinical variables improved prediction of incident dysglycemia (AROC=0.6731 vs 0.638; P < 0.05). Conclusions sCD163 was longitudinally associated with core disorders that precede the onset of type 2 diabetes.

Objective: apoA1 (apolipoprotein A-1) is the main lipoprotein associated with HDL (high-density lipoprotein) cholesterol. It was recently reported that intravenous infusion of apoA1 could lower insulin resistance in pregnant rats, leading to the suggestion that apoA1 could provide a target for reducing pregnancy-induced insulin resistance and the risk of gestational diabetes mellitus (GDM) in humans. However, the effects of apoA1 on insulin resistance and risk of GDM in human pregnancy are not known. Thus, we sought to systematically evaluate the relationships of apoA1 with glucose homeostasis and metabolic function in pregnant women. Approach and Results: In this study, 870 pregnant women were recruited in late second trimester and underwent metabolic characterization, including an oral glucose tolerance test on which 214 were diagnosed with GDM. Metabolic characterization included assessment of glucose tolerance, insulin sensitivity/resistance (Matsuda index, homeostasis model assessment of insulin resistance), pancreatic β-cell function, lipids (LDL [low-density lipoprotein] cholesterol, HDL cholesterol, triglycerides, apoB [apolipoprotein B], and apoA1), CRP (C-reactive protein), and adiponectin. Serum apoA1 was strongly correlated with HDL (r=0.79, P P =0.0004) but showed no association with measures of insulin sensitivity/resistance, β-cell function, glycemia, or CRP. There were no significant differences across apoA1 tertiles in mean adjusted Matsuda index ( P =0.24), homeostasis model assessment of insulin resistance ( P =0.08), or area under the glucose curve on the oral glucose tolerance test ( P =0.96). Moreover, there were no differences in risk of GDM across tertiles of apoA1, both before ( P =0.67) and after covariate adjustment ( P =0.78). Conclusions: Serum apoA1 is not associated with insulin resistance or the risk of GDM in human pregnancy.

BACKGROUND: Novel oils high in monounsaturated fatty acids (MUFAs) and low in saturated fatty acids (SFAs) are an alternative to partially hydrogenated oils high in trans-unsaturated fatty acids. There is widespread use of high-MUFA oils across the food industry; however, limited knowledge of their cardiovascular impact exists. OBJECTIVES: We investigated the effects of diets containing canola oil, high-oleic acid canola oil (HOCO), and a control oil blend (diet formulated to emulate a Western fat profile) on lipids, lipoproteins, and apolipoproteins (apos), as secondary outcomes of the trial. METHODS: In a multi-center, double-blind, randomized, 3-period crossover, controlled feeding trial, men (n = 44) and women (n = 75) with a mean age of 44 y, mean body mass index (BMI; in kg/m(2)) of 31.7, and an increased waist circumference plus ≥1 metabolic syndrome criteria consumed prepared, weight-maintenance diets containing canola oil [17.5% MUFAs, 9.2% polyunsaturated fatty acids (PUFAs), 6.6% SFAs], HOCO (19.1% MUFAs, 7.0% PUFAs, 6.4% SFAs), or control oil (10.5% MUFAs, 10.0% PUFAs, 12.3% SFAs) for 6 wk with ≥4-wk washouts. Fasting serum lipids were assessed at baseline and 6 wk. Diet effects were examined using a repeated measures mixed model. RESULTS: Compared with the control, canola and HOCO diets resulted in lower endpoint total cholesterol (TC; −4.2% and −3.4%; P

Aim: Our objective was to determine the association of adipose tissue insulin resistance with longitudinal changes in biomarkers of adipose tissue function, circulating lipids, and dysglycemia. Research design and methods: Adults at-risk for type 2 diabetes in the Prospective Metabolism and Islet Cell Evaluation (PROMISE) cohort had up to four assessments over 9 years (n=468). Adipose tissue insulin resistance was determined using a novel validated index, Adipo-IR, calculated as the product of fasting insulin and non-esterified fatty acids measured at baseline. Fasting serum was used to measure biomarkers of adipose tissue function (adiponectin and sCD163), circulating lipids (total cholesterol, HDL, LDL, TG), and systemic inflammation (Il-6 and TNF-α). Incident dysglycemia was defined as the onset of impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes at follow-up. Generalized estimating equation (GEE) models were used to assess the relationship of Adipo-IR with longitudinal outcomes. Results: GEE analyses showed that elevated Adipo-IR was longitudinally associated with adipose tissue dysfunction (adiponectin: -4.20% (95%CI, -6.40 to –1.95); sCD163: 4.36% (95%CI, 1.73 – 7.06), HDL (-3.87% (95%CI, -5.15 to -2.57)) and TG (9.26% (95%CI, 5.01 to 13.69)). Adipo-IR was associated with increased risk of incident dysglycemia (OR=1.59; 95%CI, 1.09 to 2.31, per SD increase). Associations remained significant after adjustment for waist circumference, and surrogate indices for insulin resistance. There were no significant longitudinal associations of Adipo-IR with Il-6, TNF-α, total cholesterol, or LDL. Conclusion: Our findings demonstrate that adipose tissue insulin resistance is prospectively associated with adipose tissue function, HDL, TG, and incident dysglycemia.

Diets varying in SFA and MUFA content can impact glycaemic control; however, whether underlying differences in genetic make-up can influence blood glucose responses to these dietary fatty acids is unknown. We examined the impact of dietary oils varying in SFA/MUFA content on changes in blood glucose levels (primary outcome) and whether these changes were modified by variants in the stearoyl-CoA desaturase (SCD) gene (secondary outcome). Obese men and women participating in the randomised, crossover, isoenergetic, controlled-feeding Canola Oil Multicenter Intervention Trial II consumed three dietary oils for 6 weeks, with washout periods of ˜6 weeks between each treatment. Diets studied included a high SFA/low MUFA Control oil (36·6 % SFA/28·2 % MUFA), a conventional canola oil (6·2 % SFA/63·1 % MUFA) and a high-oleic acid canola oil (5·8 % SFA/74·7 % MUFA). No differences in fasting blood glucose were observed following the consumption of the dietary oils. However, when stratified by SCD genotypes, significant SNP-by-treatment interactions on blood glucose response were found with additive models for rs1502593 (P = 0·01), rs3071 (P = 0·02) and rs522951 (P = 0·03). The interaction for rs3071 remained significant (P = 0·005) when analysed with a recessive model, where individuals carrying the CC genotype showed an increase (0·14 (sem 0·09) mmol/l) in blood glucose levels with the Control oil diet, but reductions in blood glucose with both MUFA oil diets. Individuals carrying the AA and AC genotypes experienced reductions in blood glucose in response to all three oils. These findings identify a potential new target for personalised nutrition approaches aimed at improving glycaemic control.

This systematic review investigates the association of sCD163, a novel biomarker of macrophage activation, with type 2 diabetes mellitus (T2DM), insulin resistance, and beta-cell dysfunction. Sixteen studies (seven cross-sectional, two case-control, one nested case-control, three prospective cohort, and three experimental) were identified. Most studies demonstrated that elevated sCD163 concentrations were associated with increased insulin resistance. Cross-sectional, case-control, and nested case-control studies showed higher sCD163 in subjects with T2DM compared with healthy individuals. An 18-year follow-up prospective cohort study showed that elevated baseline sCD163 was a strong predictor of T2DM incidence. Prospective cohort studies demonstrated that baseline measures and longitudinal changes in sCD163 were positively associated with insulin resistance; however, associations with beta-cell function were inconsistent. Two experimental studies evaluated the relationship of sCD163 with T2DM and HOMA-IR after weight-reducing interventions. After very low-calorie diet treatments, sCD163 concentration declined significantly in patients with T2DM but was not associated with insulin resistance. Bariatric surgery did not significantly impact sCD163 levels. In a double-blind randomized controlled trial, resveratrol supplementation significantly reduced circulating sCD163 in T2DM patients. Current studies demonstrate the potential utility of sCD163 as an early biomarker of T2DM risk and highlight a potential mechanism linking obesity with T2DM onset.

Worsening renal function in chronic kidney disease correlates with worsening right ventricular (RV) systolic function. We evaluated the association between kidney transplantation (KT) and RV structure and systolic function, and the relationships between RV and left ventricular (LV) changes, blood pressure, and specific cardiac biomarkers, in patients with end-stage kidney disease using cardiac magnetic resonance imaging (CMR). In this prospective, multi-centre, cohort study, 39 adult patients on dialysis receiving KT and 42 patients eligible for, but not yet receiving KT, were recruited. CMR was performed at baseline, and repeated at 12 months. Among 81 patients (mean age 51 years, 30% female), RV end-diastolic volume index (RVEDVi), end-systolic volume index (RVESVi), mass index (RVMi), and ejection fraction (RVEF) did not change significantly within either the dialysis or KT group over 12 months (all p ≥ 0.10). There were no significant differences in the 12-month changes of these parameters between the dialysis and KT groups (all p ≥ 0.10). RVMI demonstrated positive correlations with NT-proBNP and systolic blood pressure, but not GDF-15, at baseline and at 12 months. Changes in RVEDVi, RVESVi, and RVEF were positively correlated with changes in LVEDVi, LVESVi, and LVEF, respectively over 12 months (Spearman r = 0.72, 0.52, and 0.41; all p 0.001), but not mass index (Spearman r = 0.20, p = 0.078). In conclusion, there were no significant changes in RV mass, volumes, or systolic function 12 months after KT, as compared with continuation of dialysis. The associations between RV and LV remodeling may suggest similar underlying pathophysiologic mechanisms.

Increased left atrial (LA) size predicts cardiovascular events in patients with end-stage kidney disease. There is a paucity of data on LA changes after kidney transplantation (KT). Accordingly, we used cardiac magnetic resonance imaging (CMR) to evaluate LA remodeling after KT, and examined its relationship with left ventricular (LV) measurements, blood pressure and cardiac biomarkers.In this prospective multi-center cohort study, 39 pre-transplant dialysis patients underwent KT and 42 eligible transplant recipients remained on dialysis. CMR, blood pressure and serum measurements for N-terminal pro b-type natriuretic peptide (NT-proBNP), high sensitivity C-reactive protein (hsCRP), and growth differentiation factor-15 (GDF-15) were performed at baseline and 12 months.After 12 months, there were no significant changes in LA end-systolic volume index, LA end-diastolic volume index, or LA ejection fraction (LAEF) within the KT or dialysis group; changes over time did not differ between the 2 groups (all p 0.25). At baseline and over 12 months, LA volumes and LAEF positively correlated with LV volumes and mass while LAEF positively correlated with LV function. Changes in LA volumes also positively correlated with NT-proBNP and systolic blood pressure (sBP) while LAEF negatively correlated with NT-proBNP. GDF-15 correlated with LA measurements at baseline but not in 12-month changes. hsCRP did not correlate with any LA measurements.LA volumes and function as measured by CMR did not change significantly over 12 months post-KT. There were significant associations between LA and LV remodeling, NT-proBNP and sBP, suggesting common underlying pathophysiological mechanisms.

BackgroundPatients on dialysis have impaired cardiac function, in part due to increased fluid volume and ventricular stress. Restored kidney function through transplantation reduces left ventricular volume in both systole and diastole. Paraoxonase 1 (PON1) is reduced in patients on dialysis, which may be related to their impaired cardiac function. We tested the hypothesis that change in PON1 is associated with changes in left ventricular (LV) end-volume and LV mass after kidney transplantation.MethodsPatients were studied before and 12 months after kidney transplantation. The control group was patients on dialysis not expected to receive a transplant in the next 12 months. Cardiac magnetic resonance imaging was used to measure LV end-diastolic and end-systolic volume and LV mass. PON1 was measured by arylesterase activity and by mass.ResultsPON1 mass and activity were not different between the groups at baseline. Both PON1 mass and activity were increased post-kidney transplantation (p2.7) (p=0.0146 and 0.0114 for diastolic and systolic, respectively) and with the change in hemoglobin (p=0.0042).ConclusionsPON1 mass and activity increase after kidney transplantation. The increase in PON1 mass is consistent with a novel relationship to the increase in hemoglobin and the decrease in LV end-systolic and end-diastolic volume.

Background Gestational diabetes (GDM) and milder gestational impaired glucose tolerance (GIGT) identify women at risk of developing type 2 diabetes and cardiovascular disease later in life. Accordingly, the postpartum years after gestational dysglycemia can provide insight into early events in the natural history of these disorders. We thus sought to prospectively evaluate the relationship between gestational glucose tolerance and emerging cardiometabolic biomarkers [adiponectin, chemerin, retinol-binding protein-4 (RBP-4), C-reactive protein (CRP), plasminogen activator inhibitor-1 (PAI-1)] at both 1- and 3-years postpartum in a cohort reflecting the full spectrum of gestational dysglycemia (from normal to GIGT to GDM). Methods Three-hundred-and-thirty-nine women completed a glucose challenge test (GCT) and oral glucose tolerance test (OGTT) in pregnancy, which identified 4 gestational glucose tolerance groups: GDM (n = 105); GIGT (n = 59); abnormal GCT with normal OGTT (n = 99); and normal GCT with normal OGTT (n = 76). At 1- and 3-years postpartum, the women underwent repeat OGTT with measurement of biomarkers (adiponectin/chemerin/RBP-4/CRP/PAI-1). Results Serum adiponectin was lower in women with GDM and GIGT at both 1-year and 3-years (both P ≤ 0.002), whereas chemerin, RBP-4, CRP and PAI-1 showed no differences across the 4 groups. Importantly, the change in PAI-1 between 1- and 3-years progressively increased from the normal GCT group to the abnormal GCT group to GIGT to GDM (P = 0.03). Indeed, both GDM (t = 2.98, P = 0.003) and GIGT (t = 2.14, P = 0.03) independently predicted an increase in PAI-1 from 1- to 3-years postpartum. Conclusions Hypoadiponectinemia and rising PAI-1 over time are early features of the cardiometabolic biomarker profile of women with recent gestational dysglycemia. Electronic supplementary material The online version of this article (10.1186/s12933-018-0776-y) contains supplementary material, which is available to authorized users.

BACKGROUND: Cholesterol efflux plays an important role in preventing atherosclerosis progression. Vegetable oils with varying unsaturated fatty acid profiles favorably affect multiple cardiovascular disease risk factors; however, their effects on cholesterol efflux remain unclear. OBJECTIVE: The objectives of this study were to examine the effects of diets low in saturated fatty acids (SFAs) with varying unsaturated fatty acid profiles on serum-mediated cholesterol efflux and its association with the plasma lipophilic index and central obesity. METHODS: The present study is a randomized, crossover, controlled-feeding study. Participants [men: n = 50; women: n = 51; mean ± SE age: 49.5 ± 1.2 y; body mass index (in kg/m(2)): 29.4 ± 0.4] at risk for or with metabolic syndrome (MetS) were randomly assigned to 5 isocaloric diets containing the treatment oils: canola oil, high oleic acid–canola oil, DHA-enriched high oleic acid–canola oil, corn oil and safflower oil blend, and flax oil and safflower oil blend. These treatment oils were incorporated into smoothies that participants consumed 2 times/d. For a 3000-kcal diet, 60 g of treatment oil was required to provide 18% of total energy per day. Each diet period was 4 wk followed by a 2- to 4-wk washout period. We quantified cholesterol efflux capacity with a validated ex vivo high-throughput cholesterol efflux assay. Statistical analyses were performed with the use of the SAS mixed-model procedure. RESULTS: The 5 diets increased serum-mediated cholesterol efflux capacity from THP-1 macrophages similarly by 39%, 34%, 55%, 49% and 51%, respectively, compared with baseline (P

Context Circulating B-type natriuretic peptide, as measured by the N-terminal fragment of its prohormone (NT-proBNP), is inversely associated with incident type 2 diabetes (T2DM) but positively related to future cardiovascular disease (CVD). Recognizing that gestational diabetes (GDM) identifies women at future risk for both T2DM and CVD, we sought to determine whether gestational glucose tolerance relates to NT-proBNP in the years after delivery. Design/Patients/Measurements Three-hundred-and-forty women underwent a glucose challenge test (GCT) and an oral glucose tolerance test (OGTT) in pregnancy, yielding 4 gestational glucose tolerance groups: GDM (n=105); gestational impaired glucose tolerance (n=59); abnormal GCT with a normal OGTT (n=98); and normal GCT with normal OGTT (n=75). At 3-years postpartum, they underwent cardiometabolic characterization (including measurement of estimated glomerular filtration rate (eGFR), adiponectin, and NT-proBNP) and repeated the OGTT, revealing 69 women with glucose intolerance (pre-diabetes/diabetes). Results At 3-years postpartum, serum NT-proBNP did not differ between the 4 original gestational glucose tolerance groups (p=0.44), but instead progressively decreased across current glucose tolerance strata, from normal to pre-diabetes to diabetes (p=0.006). Indeed, on logistic regression analysis, NT-proBNP emerged as a negative predictor of pre-diabetes/diabetes (OR=0.903, 95%CI 0.825-0.988, p=0.026). On multiple linear regression analyses of NT-proBNP, the significant association with current glucose intolerance was ultimately attenuated in a fully-adjusted model, revealing two independent determinants of NT-proBNP: eGFR (t=-2.71, p=0.007) and adiponectin (t=2.44, p=0.015). Conclusion Serum NT-proBNP relates to current glucose intolerance, rather than preceding gestational dysglycemia. Thus, the diabetic (rather than vascular) risk implications of NT-proBNP predominate in young women. This article is protected by copyright. All rights reserved.

Aims Dysregulation of arginine metabolism, as evidenced by increased circulating levels of asymmetric dimethylarginine (ADMA), has been proposed as an early event in the natural history of cardiovascular disease. Since the diagnosis of gestational diabetes mellitus (GDM) identifies a patient population at increased future risk of cardiovascular disease later in life, we sought to characterize arginine metabolism in women with and without a history of recent GDM. Methods In this prospective observational cohort study, 225 women (72 who had GDM; 153 who did not) underwent cardiometabolic characterization, including oral glucose tolerance test, at 1- and 3-years postpartum. Circulating ADMA and its stereoisomer symmetric dimethylarginine (SDMA) were measured by liquid chromatography–mass spectrometry at both visits. Results Serum ADMA and SDMA were not significantly different between the GDM and non-GDM groups at either 1-year or 3-years postpartum. On multiple linear regression analyses, high-density-lipoprotein cholesterol (t = − 2.62, p = 0.009) and creatinine (t = − 2.62, p = 0.01) were independently associated with ADMA at 3-years, while creatinine (t = 7.09, p Conclusion Women with recent GDM do not exhibit altered serum concentrations of ADMA or SDMA at 1- and 3-years postpartum, suggesting that ADMA dysregulation is not a feature of their cardiometabolic profile in the early years after delivery.

Context Glucagon-like peptide-1 agonists acutely lower serum glucagon. However, in the Liraglutide and β-Cell Repair (LIBRA) Trial, 48-week treatment with liraglutide yielded lower/unchanged fasting glucagon but, surprisingly, enhanced postchallenge glucagonemia [measured by R&D Systems (Minneapolis, MN) assay]. Objective Because differences between glucagon assays potentially could explain these unexpected findings, we have remeasured glucagon in all 1222 samples from this trial using the highly-sensitive/specific Mercodia assay to compare the findings between assays. Design/setting/participants/intervention In LIBRA, 51 patients with type 2 diabetes of 2.6 ± 1.9 years duration were randomized to daily subcutaneous liraglutide or placebo injection and followed for 48 weeks, with serial oral glucose tolerance test (OGTT) every 12 weeks (with liraglutide/placebo last administered ∼24 hours earlier). Outcome Serum glucagon was measured every 30 minutes on each OGTT, enabling determination of the area under the glucagon curve (AUCglucagon). Results With the Mercodia assay, fasting glucagon was higher in the liraglutide arm than placebo at 12 weeks (P = 0.01), with no between-group differences at 24, 36, and 48 weeks. There was no difference in AUCglucagon between the groups at any visit. Mercodia and R&D Systems glucagon measurements correlated at postchallenge time points but not at fasting. Conclusion The Mercodia assay did not replicate the R&D Systems glucagon findings. Although neither assay demonstrated lower postchallenge glucagonemia with chronic liraglutide last administered ∼24 hours earlier, the differential response reported by these assays precludes definitive conclusion and highlights the critical role of assay selection when measuring glucagon in clinical studies.

Background The 1‐hour glucose challenge test ( GCT ) is routinely performed in pregnancy to screen for gestational diabetes mellitus. Remarkably, it has recently emerged that the GCT can also predict a woman's future risk of cardiovascular disease, although the mechanistic basis of this relationship is unclear. In this context we hypothesized that a higher GCT may identify women with an otherwise unrecognized adverse cardiovascular phenotype. Thus, we sought to evaluate the relationship between the antepartum GCT and subsequent postpartum cardiovascular risk factor profile. Methods and Results In this study 503 women completed a screening GCT in late second trimester and then underwent cardiometabolic characterization at 3 months postpartum, whereupon traditional (blood pressure, glucose, lipids) and nontraditional (apolipoprotein B, C‐reactive protein, adiponectin) cardiovascular risk factors were compared across GCT tertiles. At 3 months postpartum, each of the following risk factors progressively worsened from the lowest to middle to highest GCT tertile: fasting glucose ( P =0.0002), 2‐hour glucose ( P P =0.0004), high‐density lipoprotein cholesterol ( P =0.004), triglycerides ( P =0.001), apolipoprotein B ( P =0.001), and adiponectin ( P =0.02). On multiple linear regression analyses, the GCT emerged as a significant independent predictor of higher fasting glucose ( P =0.0006), 2‐hour glucose ( P P =0.0004), triglycerides ( P =0.001), low‐density lipoprotein cholesterol ( P =0.01), and apolipoprotein B ( P =0.004) and of lower high‐density lipoprotein cholesterol ( P =0.02) and adiponectin ( P =0.0099). Moreover, these independent associations persisted after excluding women who had gestational diabetes mellitus. Conclusions The antepartum GCT can identify women with an adverse underlying cardiovascular risk factor phenotype.

ObjectiveTo evaluate multiple determinants of the longitudinal change in insulin clearance (IC) in subjects at high risk for type 2 diabetes (T2D).Research design and methodsAdults (n=492) at risk for T2D in the Prospective Metabolism and Islet Cell Evaluation cohort, a longitudinal observational cohort, had four visits over 9 years. Values from oral glucose tolerance tests collected at each assessment were used to calculate the ratios of both fasting C peptide-to-insulin (ICFASTING) and areas under the curve of C peptide-to-insulin (ICAUC). Generalized estimating equations (GEE) evaluated multiple determinants of longitudinal changes in IC.ResultsIC declined by 20% over the 9-year follow-up period (pFASTING and ICAUC over time (all pConclusionsOur findings suggest that non-European ethnicity and components of the metabolic syndrome, including central obesity, non-alcoholic fatty liver disease, and subclinical inflammation, may be related to longitudinal declines in IC.

Background Cardiovascular disease is a significant cause of morbidity and mortality in patients with end-stage renal disease (ESRD) and kidney transplant (KT) patients. Compared with left ventricular (LV) ejection fraction (LVEF), LV strain has emerged as an important marker of LV function as it is less load dependent. We sought to evaluate changes in LV strain using cardiovascular magnetic resonance imaging (CMR) in ESRD patients who received KT, to determine whether KT may improve LV function. Methods We conducted a prospective multi-centre longitudinal study of 79 ESRD patients (40 on dialysis, 39 underwent KT). CMR was performed at baseline and at 12 months after KT. Results Among 79 participants (mean age 55 years; 30% women), KT patients had significant improvement in global circumferential strain (GCS) (p = 0.007) and global radial strain (GRS) (p = 0.003), but a decline in global longitudinal strain (GLS) over 12 months (p = 0.026), while no significant change in any LV strain was observed in the ongoing dialysis group. For KT patients, the improvement in LV strain paralleled improvement in LVEF (57.4 ± 6.4% at baseline, 60.6% ± 6.9% at 12 months; p = 0.001). For entire cohort, over 12 months, change in LVEF was significantly correlated with change in GCS (Spearman’s r = − 0.42, p 0.10). Conclusions Compared with continuation of dialysis, KT was associated with significant improvements in LV strain metrics of GCS and GRS after 12 months, which did not correlate with blood pressure change. This supports the notion that KT has favorable effects on LV function beyond volume and blood pessure control. Larger studies with longer follow-up are needed to confirm these findings. Electronic supplementary material The online version of this article (10.1186/s12968-018-0504-5) contains supplementary material, which is available to authorized users.

Objective To determine the effect of diets low in saturated fatty acids and high in monounsaturated fatty acids (MUFA) or polyunsaturated fatty acids on body composition in participants at risk for metabolic syndrome (MetS). Methods This study was a randomized, crossover, controlled feeding study. Participants (n = 101, ages 49.5 ± 1.2, BMI 29.4 ± 0.4 kg/m2) were randomized to five isocaloric diets containing treatment oils: Canola, CanolaOleic, CanolaDHA, Corn/Safflower, and Flax/Safflower. Each diet period was 4 weeks followed by a 2- to 4-week washout period. Results Canola (3.1 kg, P = 0.026) and CanolaOleic oil diets (3.09 kg, P = 0.03) reduced android fat mass compared with the Flax/Saff oil diet (3.2 kg), particularly in men. The decrease in abdominal fat mass was correlated with the reduction in blood pressure after the Canola (systolic blood pressure: r = 0.26, P = 0.062; diastolic blood pressure: r = 0.38, P = 0.0049) and CanolaOleic oil diets (systolic blood pressure: r = 0.39 P = 0.004; diastolic blood pressure: r = 0.45, P = 0.0006). The decrease in abdominal fat mass also was associated with a reduction in triglyceride levels after the CanolaOleic oil diet (r = 0.42, P = 0.002). Conclusions Diets high in MUFA (compared with PUFA) reduced central obesity with an accompanying improvement in MetS risk factors. Diets high in MUFA may be beneficial for treating and perhaps preventing MetS.

Gestational diabetes (GDM) arises in women in whom there is insufficient β-cell compensation for the insulin resistance of late pregnancy. The mechanisms underlying both normal antepartum β-cell adaptation and its aberrancy in GDM are unclear. Preclinical studies have suggested that the hormones prolactin and human placental lactogen (HPL) may stimulate β-cell mass, whereas the furan fatty acid metabolite 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) has recently emerged as a potential negative regulator of β-cell function. However, there has been limited study of these factors in humans.Our objective was to systematically evaluate HPL, prolactin, and CMPF in relation to glucose homeostasis and β-cell function in women with and without GDM.Three-hundred-and-ninety-five women underwent an oral glucose tolerance test in late pregnancy, enabling assessment of GDM status, glycemia (area-under-the-glucose-curve on oral glucose tolerance test [AUCglucose]), β-cell function (Insulin Secretion-Sensitivity Index-2, insulinogenic index/homeostatic model assessment of insulin resistance [HOMA-IR]), insulin sensitivity/resistance (Matsuda index, HOMA-IR), and circulating HPL, prolactin, and CMPF.Serum concentrations of HPL, prolactin, and CMPF were similar between women with GDM (n = 105) and women without GDM (n = 290). However, on multiple linear regression analyses, CMPF emerged as a significant predictor of AUCglucose in women with GDM (t = 4.75, P.0001) but not in their peers (P = .60). Furthermore, CMPF independently predicted lower Insulin Secretion-Sensitivity Index-2 (t = -2.28, P = .02) and lower insulinogenic index/HOMA-IR (t = -2.22, P = .03) in women with GDM but not in the non-GDM group (both P = .93). Neither HPL nor prolactin was significantly associated with AUCglucose, β-cell function, or insulin sensitivity.CMPF is a potential circulating determinant of β-cell dysfunction and hyperglycemia in women with GDM.

There is debate about whether women may need greater vitamin D supplementation when pregnant. However, it is unclear whether the 25-hydroxyvitamin D (25-OH-D) concentration required for suppression of PTH (ie, suggesting vitamin D sufficiency) differs between pregnancy and the nongravid state.To systematically characterize the relationship between 25-OH-D and PTH during and after pregnancy.In this study, 468 women underwent serial assessment of serum 25-OH-D and PTH in late pregnancy, at 3 months postpartum, and at 12 months postpartum. At each visit, segmented regression analysis was performed to: 1) determine the best model to fit the relationship between 25-OH-D and PTH; and 2) identify the 25-OH-D threshold above which PTH is maximally suppressed.Serum 25-OH-D and PTH were inversely correlated at each of the pregnancy (r = −0.33; P.0001), 3 months postpartum (r = −0.37; P.0001), and 12 months postpartum (r = −0.34; P.0001) assessments. In pregnancy, PTH first rises when 25-OH-D falls below 82 nmol/L (95% confidence interval, 61–103) and follows a linear relationship with declining 25-OH-D thereafter. In contrast, at both postpartum visits, there was a curvilinear relationship between 25-OH-D and PTH below the 25-OH-D threshold at which PTH is suppressed (71 nmol/L [61–81] at 3 months and 81 nmol/L [61–100] at 12 months). The 25-OH-D thresholds for PTH suppression in pregnancy and at 3 and 12 months postpartum were not significantly different from one another (all pairwise P ≥ .26).Although the shape of the relationship between 25-OH-D and PTH differs between pregnancy and the postpartum, the 25-OH-D thresholds for PTH suppression are similar, supporting comparable targets for vitamin D supplementation.

SummaryBackground Pregnancy and lactation comprise a critical window spanning all seasons during which maternal vitamin D status potentially may influence the long-term health of the newborn. Women typically receive calcium/vitamin D supplementation through antenatal vitamins, but there has been limited serial evaluation of maternal vitamin D status across this critical window. Design/Patients/Measurements In this prospective observational cohort study, 467 women in Toronto, Canada, underwent measurement of serum 25-hydroxy vitamin D (25-OH-D) at mean 29·7 ± 2·9 weeks' gestation, 3 months postpartum and 12 months postpartum, enabling serial assessment across 3 seasons. At each assessment, vitamin D status was classified as deficiency (25-OH-D

Platelet αIIbβ3 integrin and its ligands are essential for thrombosis and hemostasis, and play key roles in myocardial infarction and stroke. Here we show that apolipoprotein A-IV (apoA-IV) can be isolated from human blood plasma using platelet β3 integrin-coated beads. Binding of apoA-IV to platelets requires activation of αIIbβ3 integrin, and the direct apoA-IV-αIIbβ3 interaction can be detected using a single-molecule Biomembrane Force Probe. We identify that aspartic acids 5 and 13 at the N-terminus of apoA-IV are required for binding to αIIbβ3 integrin, which is additionally modulated by apoA-IV C-terminus via intra-molecular interactions. ApoA-IV inhibits platelet aggregation and postprandial platelet hyperactivity. Human apoA-IV plasma levels show a circadian rhythm that negatively correlates with platelet aggregation and cardiovascular events. Thus, we identify apoA-IV as a novel ligand of αIIbβ3 integrin and an endogenous inhibitor of thrombosis, establishing a link between lipoprotein metabolism and cardiovascular diseases., Activation of integrin αIIbβ3 at the surface of platelets is required for their aggregation and for thrombus formation. Here Xu et al. identify apolipoprotein A-IV as a novel ligand for platelet αIIbβ3 integrin, and find it inhibits platelet aggregation and thrombosis.

ObjectiveWomen with a history of gestational diabetes mellitus (GDM) have an elevated risk of ultimately developing pre-diabetes and diabetes later in life. They also have an increased prevalence of fatty liver, but recent studies have reported conflicting findings on whether hepatic fat affects their risk of pre-diabetes/diabetes. Thus, we sought to evaluate the associations of liver fat with glucose homeostasis and determinants thereof in women with and without recent gestational dysglycemia.MethodsTwo hundred and fifty-seven women underwent an antepartum oral glucose tolerance test (OGTT), which diagnosed 97 with GDM, 40 with gestational impaired glucose tolerance (GIGT), and 120 with normal glucose tolerance (NGT). At a mean of 4.8 years post partum, they underwent an OGTT (which revealed that 52 had progressed to pre-diabetes/diabetes) and hepatic ultrasound, on which liver fat was graded as none (n=164), mild (n=66), or moderate (n=27).ResultsLiver fat was more prevalent in women with previous GDM than in those with GIGT or NGT (p=0.009) and in women with current pre-diabetes/diabetes than in those without (p=0.0003). As the severity of liver fat increased, there was a progressive worsening of insulin sensitivity and beta-cell function, coupled with rising fasting and 2-hour glucose (all pConclusionThe higher prevalence of liver fat in women with previous GDM is associated with their increased risk of pre-diabetes/diabetes.