Chang Ye's research while affiliated with University of Toronto and other places
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Publications (63)
Background
The cumulative effect of postpartum weight retention from each pregnancy in a woman’s life may contribute to her risk of ultimately developing type 2 diabetes and cardiovascular disease. However, there is limited direct evidence supporting this hypothesis. Thus, we sought to characterize the impact of postpartum weight retention on the t...
Aims/hypothesis:
Excess adiposity, insulin resistance and beta cell dysfunction each contribute to the development of prediabetes (impaired glucose tolerance and/or impaired fasting glucose)/diabetes but their comparative impact in relation to one another remains uncertain. We thus ranked their contributions to incident dysglycaemia over the first...
The cumulative effect of postpartum weight retention from each pregnancy in a woman’s life may contribute to her risk of ultimately developing cardiovascular (CV) disease and type 2 diabetes. However, there is limited direct evidence supporting this hypothesis. Thus, we sought to characterize the impact of postpartum weight retention on the traject...
Objective
Basal insulin glargine has a neutral effect on cardiovascular risk in type 2 diabetes (T2DM). In practice, basal insulin is often paired with a glucagon-like peptide-1 receptor agonist (GLP1-RA) or meal insulin; however, the cardiovascular implications of these combinations have not been fully elucidated. In this context, we sought to eva...
Objective:
To compare postpartum glucose tolerance between women treated for gestational diabetes mellitus (GDM) and those not treated.
Research design and methods:
Metabolic 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 o...
In clinical research, weight measurement in first trimester is often treated as a surrogate for pre-pregnancy weight. The validity of this critical assumption, however, is uncertain. Thus, we sought to prospectively evaluate the relationship between pre-gravid weight and first trimester weight. In this prospective preconception observational cohort...
Combining a glucagon-like peptide-1 receptor agonist (GLP1-RA) with basal insulin is an emerging option when initiating injectable therapy in longstanding type 2 diabetes (T2DM). Recognizing that short-term insulin therapy can improve beta-cell function and induce glycemic remission in early T2DM, we hypothesized that adding the short-acting GLP1-R...
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 child...
This cohort study evaluates the associations of preconception paternal smoking with neonatal outcomes.
Importance
Several studies have shown that older married couples share a propensity for accruing the same cardiovascular risk factors such as hypertension and dyslipidemia. However, it remains unclear if these spousal associations reflect their shared home environment and lifestyle or the tendency to choose a partner with a similar perspective on l...
Abstract Background/Objective Previous studies have consistently demonstrated that maternal weight status both before and during pregnancy is associated with infant birthweight. However, a fundamental limitation across this literature remains that previous studies have not evaluated the concomitant impact of paternal weight at conception, owing to...
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 var...
Aims:
When administered in early T2DM, short-term intensive insulin therapy (IIT) can improve reversible beta-cell dysfunction and induce remission of diabetes, but these effects are not permanent. To preserve beta-cell function, we have previously suggested that "induction" IIT should be followed by a "maintenance therapy", such as metformin. Her...
Background: Women with a history of certain adverse outcomes in pregnancy (preterm birth, delivery of a small-for-gestational age [SGA] infant, preeclampsia, and gestational diabetes mellitus [GDM]) have an elevated lifetime prevalence of metabolic syndrome (MetS) and cardiovascular disease, compared with their peers. However, it is not known if Me...
Amid growing recognition of the Developmental Origins of Health and Disease, maternal recall of infant birth weight has emerged as a mainstay of clinical research associating fetal exposures with subsequent health in childhood. Since studies at various offspring ages have noted the accuracy of maternal report of birth weight,¹⁻³ it is widely assume...
Objectives
The sex ratio at birth (proportion of boys to girls) generally shows slight male preponderance but may decrease in response to societal stressors. Discrete adverse events such as terrorist attacks and disasters typically lead to a temporary decline in the sex ratio 3–5 months later, followed by resolution over around 5 months thereafter....
Objective
Higher neighborhood walkability has been associated with a lower risk of type 2 diabetes mellitus (T2DM) by promoting greater physical activity (thereby reducing weight and lowering insulin resistance). However, it is not known if walkability may similarly reduce maternal risk of gestational diabetes mellitus (GDM), which arises in the se...
Context
Serum 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.
Objective
To evaluate the impact of change...
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...
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...
Objective:
In early type 2 diabetes (T2DM), the administration of short-term intensive insulin therapy (IIT) can induce glycemic remission for a year thereafter, but this effect ultimately wanes. In this context, intermittently repeating short-term IIT could provide a strategy for maintaining the otherwise transient benefits of this intervention. H...
Women with a history of adverse outcomes in pregnancy (including pre-term birth, delivery of a small-for-gestational-age (SGA) infant, preeclampsia, and gestational diabetes (GDM)) have a higher prevalence of metabolic syndrome (MetS) and cardiovascular disease, as compared to their peers. However, it is not known if MetS precedes the index pregnan...
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 no...
Aims/hypothesisThe prevalence of gestational diabetes (GDM) is higher in summer months, possibly reflecting an association between ambient temperature and blood glucose levels. However, the specific exposure and mechanism by which temperature may affect glucose metabolism in pregnancy remains unclear. We systematically evaluated the relationships o...
The current era of large‐scale clinical trials in diabetes has generated thousands of biological samples from study participants that are being stored long‐term under frozen conditions for the future measurement of analytes of interest. Insulin and C‐peptide are two such analytes that can provide insight into underlying pathophysiologic processes (...
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...
Objective:
Women with gestational diabetes mellitus and milder gestational impaired glucose intolerance have elevated future risks of type 2 diabetes and cardiovascular disease. However, it is unclear whether they show postpartum evidence of vascular injury/dysfunction, an early event in the natural history of cardiovascular disease.
Methods:
In...
Objectives:
The authors conducted a systematic review and network meta-analysis of placebo-controlled, randomized clinical trials in the post-Food and Drug Administration (FDA) guidance era to formally compare the effects of 3 new classes of glucose-lowering drugs on hospitalization for heart failure (HF) in type 2 diabetes mellitus.
Background:...
Objective
Women 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...
Context
Serum concentrations of liver enzymes and the hepatokine fetuin-A have been linked to risk of type 2 diabetes, but their longitudinal impact on insulin resistance and beta-cell dysfunction is unclear
Objective
To evaluate the impact of changes over 2-years in fetuin-A and the liver enzymes alanine aminotransferase (ALT), aspartate aminotra...
Importance
Gestational weight gain is a determinant of infant birth weight, but it is unclear whether its timing in pregnancy may hold implications in this regard. Previous studies have yielded conflicting findings on the association of maternal weight gain in early pregnancy with birth weight. However, as these studies have typically recruited wom...
Aims:
When administered in early type 2 diabetes (T2DM), short-term intensive insulin therapy (IIT) can improve reversible beta-cell dysfunction and induce subsequent remission of diabetes. However, this remission is ultimately temporary, as beta-cell function deteriorates over time after stopping IIT. Thus, to preserve beta-cell function, we hypo...
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 soug...
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 d...
Background:
Population-level sociologic studies have suggested that adverse societal conditions may affect fetal viability in a sex-specific manner and thereby modify the ratio of male vs. female babies. This concept suggests that there may exist certain physiologic features in a woman that relate to her likelihood of delivering a boy or girl. We...
Breastfeeding ≥12 months is recommended for optimal infant nutrition but may hold maternal benefits, as well. Indeed, lactation has been associated with lower long-term risk of diabetes in the mother but the mechanism by which it imparts sustained post-weaning effects on glucose tolerance remains unclear. In this context, we postulated that lactati...
Objective:
The insulin resistance of mid- to late pregnancy poses a physiologic stress test for the pancreatic β-cells, which must respond by markedly increasing their secretion of insulin. This response is achieved through an expansion of β-cell mass induced by the hormones prolactin and human placental lactogen (HPL). Conversely, the furan fatty...
Context:
Gestational diabetes (GDM) arises in women in whom there is insufficient beta-cell compensation for the insulin resistance of late pregnancy. The mechanisms underlying both normal antepartum beta-cell adaptation and its aberrancy in GDM are unclear. Pre-clinical studies have suggested that the hormones prolactin and human placental lactog...
Context:
There is debate about whether women may need greater vitamin D supplementation when pregnant. However, it is unclear whether the 25-hydroxy vitamin D (25-OH-D) concentration required for suppression of parathyroid hormone (PTH) (i.e. suggesting vitamin D sufficiency) differs between pregnancy and the non-gravid state.
Objective:
To syst...
Background:
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 acro...
On cross-sectional assessment, a delayed timing of the peak blood glucose level at ≥60 min post-challenge on an OGTT is associated with beta cell dysfunction. In this context, we hypothesised that longitudinal changes in the timing of this peak might predict changes in glucose metabolism. We thus sought to evaluate the longitudinal associations of...
Retrospective analyses of perinatal databases have raised the intriguing possibility of an increased risk of gestational diabetes mellitus (GDM) in women carrying a male fetus, but it has been unclear if this was a spurious association. We thus sought to evaluate the relationship between fetal sex and maternal glucose metabolism in a well-character...
Objective:
Disruption of the gut microbiome has been associated with overweight/obesity, insulin resistance, and type 2 diabetes. Recently, it has been reported that Caesarean section disrupts the normal gut microbiome of neonates. As such, these data have raised the intriguing possibility that CS could lead to an adverse cardiometabolic risk prof...
Aims/Background
Recently, there has been considerable interest in the potential anti-diabetic effects of erythropoietin in animal models. It is not known, however, whether endogenous erythropoietin is associated with glucose regulation in humans.
Methods
We evaluated the longitudinal relationship between endogenous erythropoietin at 3-months postp...
OBJECTIVE
The cumulative effect of postpartum weight retention from each pregnancy in a woman's life may contribute to her ultimate risk of diabetes and vascular disease. However, there is little direct evidence supporting this hypothesis. In this context, we sought to evaluate the cardiometabolic implications of patterns of postpartum weight chang...
Rapid weight gain in the first 3-months of life has been associated with an unfavorable cardio-metabolic phenotype in adulthood. However, little is known about the antepartum determinants of this rapid weight gain, which may reflect key developmental exposures that program metabolic pathways. Thus, we sought to characterize the antepartum determina...
Objective:
A common approach to screening for glucose intolerance in pregnant women is the use of a 50g glucose challenge test (GCT) in the late second trimester, followed by a diagnostic oral glucose tolerance test (OGTT) when the GCT is positive (1-hour post-challenge blood glucose ≥ 7.8 mmol/L). As women with a negative GCT do not undergo the d...
As ethnicity is typically recorded as a single demographic variable in clinical studies, little is known about the relative impact of maternal vs. paternal ethnicity on fat distribution.
The objective of this study was to determine whether there is a differential impact of maternal and paternal ethnicity on infant adiposity.
Three hundred fifty-fiv...
Background:
Infants are at risk of vitamin D insufficiency, owing to their limited exposure to direct sunlight and the low levels of vitamin D in breast milk. Although vitamin D insufficiency has been associated with cardiometabolic risk factors in children, these associations have not been studied in infants, despite their unique risks. Therefore...
Objective:
A common approach to screening for gestational diabetes mellitus (GDM) is the testing of all pregnant women with a one-hour, 50 g glucose challenge test (GCT), followed by a diagnostic oral glucose tolerance test (OGTT) when the GCT is positive (≥ 7.8 mmol/L). As only a small subset of those with a positive GCT will have GDM, many more...
We thank Dokus and Dokusova (1) for their interest in our recent article on circadian variation in the response to the glucose challenge test (GCT) in pregnancy and its implications for screening for gestational diabetes mellitus (GDM) (2). In this study, 927 pregnant women with a positive GCT underwent metabolic characterization with a 3 h 100-g o...
A common approach to screening for gestational diabetes mellitus (GDM) is the universal testing of all pregnant women with a 1-h, 50-g glucose challenge test (GCT), followed by a diagnostic oral glucose tolerance test (OGTT) in those in whom the GCT is positive (≥7.8 mmol/L). More important, the GCT is performed at any time of day, but there has be...
The offspring of women with gestational diabetes mellitus (GDM) display a propensity for the early accrual of cardiometabolic risk factors, including insulin resistance, in childhood and adolescence. Thus, we sought to identify early life determinants of insulin resistance in infants of women with and without GDM.
In total, 104 full-term, singleton...
The delivery of excess maternal nutrients to the fetus is known to increase the risk of macrosomia, even among infants of women without gestational diabetes mellitus. With the current obesity epidemic, maternal adiposity and its associated effects on circulating adipokines and inflammatory proteins may now have a greater impact on fetal growth. We...
Gestational diabetes mellitus (GDM) is associated with fetal macrosomia and maternal postpartum dysglycemia, insulin resistance, and β-cell dysfunction. Indeed, in practice, a prior pregnancy that resulted in a large-for-gestational-age (LGA) delivery is often considered presumptive evidence of GDM, whether or not it was diagnosed at the time. If t...
OBJECTIVE
The increased risk of type 2 diabetes in women with glucose intolerance in pregnancy is mediated by deterioration of their β-cell function, which occurs as early as the first year postpartum. We thus sought to identify early determinants of their declining β-cell function.
RESEARCH DESIGN AND METHODS
Women with recent gestational glucose...
Citations
... This study was performed in the setting of a prospective observational cohort wherein pregnant women have been recruited at our institution to undergo serial cardiometabolic characterization in the years after delivery. The study protocol has been previously described in detail [14]. In brief, all pregnant women at our centre are screened for gestational diabetes mellitus (GDM) by 50 g glucose challenge test (GCT) at 24-28 weeks gestation, followed by oral glucose tolerance test (OGTT) in those in whom the GCT is abnormal (plasma glucose ≥ 7.8 mmol/l at 1-hour post-challenge). ...
... Indeed, previous work from our cohort has consistently demonstrated lower birthweight of infants born to women with GDM, compared to those with normal or milder dysglycemia during pregnancy, which indicates excellent glycemic control in this GDM cohort during pregnancy. 82 Three terms were significantly enriched in infants delivered through C-section: translation, glycolytic process, and tricarboxylic acid cycle. The enrichment of two carbohydrate metabolismrelated terms together with translation, which correlates with cell growth, 83 suggest that there may be a relative increase in microbial cell proliferation in infants delivered through C-section compared to vaginally delivered infants. ...
... The actual measured weight in the first trimester was used as a surrogate for recalled prepregnancy weight [33], and participants' pre-pregnancy body mass index (BMI) was calculated by the researcher. According to the BMI classification standard in China [34], the women were classified as underweight (BMI <18.5 kg/m 2 ), normal weight (BMI ¼ 18.5-23.9 ...
... 22-24 ISSI-2 exhibits stronger correlation with the disposition index from the ivGTT than do other OGTT-derived measures of betacell function (including the Homeostasis Model of Assessment) 23 and has been widely used to measure beta-cell compensation in previous clinical trials and observational studies. 18,19,[25][26][27][28] A second measure of betacell compensation was provided by the insulinogenic index/HOMA-IR. 19 The formulae for all 4 indices are provided in Online Table 1. ...
... The primary finding in BabyGEMS that fat mass at age 5.2 months was not different among groups was contrary to the study hypothesis. The lack of difference in infancy fat mass was not unexpected, as in the limited studies among infants exposed to GDM reporting on body composition differences, there are conflicting findings (21)(22)(23). Evidence from a number of longitudinal studies of offspring exposed to GDM indicates that adiposity differences emerge in the peri-pubertal years (8,24,25). ...
... Another study investigating the effect of maternal smoking during pregnancy on newborn anthropometric measurements reported that water pipe smoking during pregnancy can lead to a reduction in these measurements [8]. However, a cohort study analyzing the possible effects of paternal smoking on neonatal outcomes found no association between paternal smoking and lower birth weight [43]. ...
... Furthermore, a systematic review suggested that both health behaviors and health behavior changes were generally more consistent among couples than among individuals in the general population (38). Even newly-married partners who lived together for a short time shared clear correlations in cardiovascular risk factors and were positively associated with depressive symptoms (39). According to the interpersonal theory of depression, people with depressive symptoms are affected and influenced by their interactions with others (40). ...
... Paternal and maternal weight might affect neona-tal outcomes, but the contribution of paternal BMI is unclear. In a singleton cohort study, paternal BMI was only moderately associated with infant weight, in contrast to the dominant effect of maternal weight [9]. However, in frozen-thawed embryo transfer (FET) cycles, paternal BMI was an independent risk factor for singleton neonatal weight, with overweight and obesity associated with risks of macrosomia, LGA, and very ...
... 8,11 Previous studies have used biomarkers to classify GDM into subtypes, such as homeostatic model assessment based on fasting glucose and insulin measures, the Matsuda insulin sensitivity index, and genotyping biomarkers. 12,13 Regardless of the method used, these studies have consistently identified similar groups in terms of the underlying pathways and distribution prevalence. Women with an insulin sensitivity defect (GDM-Sensitivity) often share phenotypic characteristics with those diagnosed with type 2 diabetes, particularly those with severe insulin-resistant diabetes. ...
... Thus, there is currently interest in developing treatment strategies that can achieve the sustained stabilization of beta-cell function in early T2DM and understanding the underlying determinants of this effect 8,9 . Here we show that one such strategy is the administration of initial short-term IIT (as induction therapy) followed by metformin (as maintenance therapy), an approach that has been shown to stabilize beta-cell function for 2-years in some patients but not others 10,11 . We recently reported the main findings of the REmission Studies Evaluating Type 2 Diabetes -Intermittent Insulin Therapy Main (RESET-IT Main) trial, which demonstrated that the addition of intermittent courses of IIT does not further enhance the beneficial effect on betacell function achieved with initial induction IIT followed by metformin maintenance 11 . ...
