Leadership Sinai Center for Diabetes

Toronto, Canada

Leadership Sinai Center for Diabetes

Toronto, Canada
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Ley S.H.,University of Toronto | Harris S.B.,University of Western Ontario | Connelly P.W.,University of Toronto | Connelly P.W.,Li Ka Shing Knowledge Institute | And 10 more authors.
Clinical Chemistry | Year: 2010

BACKGROUND: Expanding evidence indicates that apolipoprotein B (apo B) is superior to LDL cholesterol as a marker of vascular disease. Although traditional lipid measures are known to predict type 2 diabetes, limited data are available regarding apo B. We assessed the association of apo B with incident type 2 diabetes and compared it with traditional lipid variables as a risk predictor in aboriginal Canadians. METHODS: Of an initial cohort of 606 individuals without diabetes in 1993-1995, 540 were contacted for the 10-year follow-up evaluation in 2003-2005. Fasting and 2-h postload glucose concentrations were obtained at baseline and follow-up to determine incident type 2 diabetes. Baseline fasting serum lipids were measured with standard laboratory procedures. RESULTS: The cumulative 10-year incidence of type 2 diabetes was 17.5%. High concentrations of apo B, triglycerides, triglycerides, and LDL cholesterol, and low concentrations of HDL cholesterol were individually associated with incident type 2 diabetes in univariate analyses. Comparing C statistics of univariate models showed apo B to be a superior determinant of incident diabetes compared with LDL (P = 0.026) or HDL (P = 0.004) cholesterol. With multivariate adjustment including waist circumference, apo B (odds ratio, 1.50; 95% CI, 1.11-2.02) and triglycerides (odds ratio, 1.49; 95% CI, 1.12-1.98) remained associated with incident diabetes, whereas LDL and HDL cholesterol became nonsignificant. CONCLUSIONS: The association of plasma apo B with incident type 2 diabetes and its better prediction of risk compared with LDL or HDL cholesterol suggest the potential for the use of apo B in type 2 diabetes risk communication and prevention.


Zinman B.,Samuel Lunenfeld Research Institute | Zinman B.,Leadership Sinai Center for Diabetes
Diabetes, Obesity and Metabolism | Year: 2013

Basal insulin analog therapy is the most common method of introducing insulin replacement therapy for the majority of patients with type 2 diabetes mellitus. Long-acting insulin analogs provide relatively peakless and more physiologic insulin replacement therapy than neutral protaminated Hagedorn insulin. Recently 2 new basal insulin analogs have been developed with superior pharmacokinetic and pharmacodynamics properties; insulin degludec and a pegylated insulin lispro. These agents are generally well tolerated and have been evaluated in both type 1 and type 2 diabetes. In this article we review the results of clinical trials assessing the efficacy, safety and tolerability of these newer longer-acting insulin analogs. In general rates of hypoglycaemia in these trials were low, glucose control was comparable to currently available basal insulin analogs, and rates of nocturnal hypoglycaemia were significantly and substantially lower. While further study will be required, advances in basal insulin replacement may offer important advantages over existing options for starting insulin strategies. © 2013 Blackwell Publishing Ltd.


Retnakaran R.,Leadership Sinai Center for Diabetes | Retnakaran R.,University of Toronto | Qi Y.,Leadership Sinai Center for Diabetes | Sermer M.,Mount Sinai Hospital | And 6 more authors.
Nutrition, Metabolism and Cardiovascular Diseases | Year: 2011

Background and aims: Women with gestational diabetes mellitus (GDM) have an enhanced cardiovascular risk factor profile at 3-months postpartum and an elevated risk of future cardiovascular disease, as compared to their peers. Recently, it has emerged that even mild dysglycemia on antepartum oral glucose tolerance test (OGTT) predicts an increased risk of future cardiovascular disease, although it is not known whether there exists an identifiable high-risk subgroup within this patient population. Since gestational impaired glucose tolerance (GIGT) due to isolated hyperglycemia at 1-h during the OGTT (1-h GIGT) bears metabolic similarity to GDM, we hypothesized that, like GDM, 1-h GIGT may predict a high-risk postpartum cardiovascular phenotype. Methods and results: In this prospective cohort study, 485 women underwent antepartum OGTT, followed by cardiovascular risk factor assessment at 3-months postpartum. The antepartum OGTT identified 4 gestational glucose tolerance groups: GDM (n = 137); 1-h GIGT (n = 39); GIGT at 2- or 3-h (2/3-h GIGT)(n = 50); and normal glucose tolerance (NGT)(n = 259). After adjustment for age, ethnicity, breastfeeding and waist circumference, mean levels of the following cardiovascular risk factors progressively increased from NGT to 2/3-h GIGT to 1-h GIGT to GDM: LDL cholesterol (p = 0.0026); total cholesterol:HDL (p = 0.0030); apolipoprotein B (p = 0.004); apolipoprotein B:apolipoprotein A1 (p = 0.026); leptin (p = 0.018); and C-reactive protein (p = 0.011). Conclusions: Amongst women without GDM, 1-h GIGT predicts an enhanced postpartum cardiovascular risk factor profile. It thus emerges, that amongst young women with mild dysglycemia in pregnancy, those with 1-h GIGT may comprise an unrecognized patient population at risk for future cardiovascular disease. © 2011 Elsevier B.V.


PubMed | Leadership Sinai Center for Diabetes
Type: Journal Article | Journal: The Journal of clinical endocrinology and metabolism | Year: 2010

Both gestational diabetes mellitus (GDM) and gestational impaired glucose tolerance (GIGT) identify women at risk of future cardiovascular disease, although the mediators of this risk are unknown. Because lipid factors can contribute to cardiovascular risk, we sought to characterize the relationship between gestational glucose tolerance status and lipid profile in pregnancy and the postpartum.Fasting lipids were measured in 482 women in pregnancy and at 3 months postpartum. Antepartum glucose challenge test (GCT) and oral glucose tolerance test (OGTT) defined four gestational glucose tolerance groups: GDM (n = 136), GIGT (n = 89), abnormal GCT with normal glucose tolerance (NGT) on OGTT (abnormal GCT NGT) (n = 170), and normal GCT with NGT on OGTT (normal GCT NGT) (n = 87).In pregnancy, there were no significant differences between the groups in total and low-density lipoprotein (LDL) cholesterol, triglycerides, total cholesterol to high-density lipoprotein (HDL) cholesterol ratio, apolipoprotein B (apoB), apolipoprotein A1 (apoA1), and apoB to apoA1 ratio. At 3 months postpartum, however, each of the following lipid parameters progressively increased from normal GCT NGT to abnormal GCT NGT to GIGT to GDM: total cholesterol (P = 0.0047), LDL (P = 0.0002), triglycerides (P = 0.0002), total cholesterol to HDL ratio (P < 0.0001), apoB (P = 0.0003), and apoB to apoA1 ratio (P = 0.0014). Furthermore, on multiple linear regression analyses, GDM emerged as an independent predictor of postpartum total cholesterol (t = 3.09, P = 0.0021), LDL (t = 3.81, P = 0.0002), triglycerides (t = 3.38, P = 0.0008), total cholesterol to HDL ratio (t = 3.76,P = 0.0002), apoB (t = 4.12, P < 0.0001), and apoB to apoA1 ratio (t = 3.07, P = 0.0023). GIGT was an independent predictor of postpartum total cholesterol to HDL ratio (t = 2.27, P = 0.0239), apoB (t = 2.04, P = 0.0416), and apoB to apoA1 ratio (t = 1.97, P = 0.049).Compared with their peers, women with GDM and GIGT have a more atherogenic lipid profile by 3 months postpartum, characterized by increased LDL and apoB.


PubMed | Leadership Sinai Center for Diabetes
Type: Journal Article | Journal: The Journal of clinical endocrinology and metabolism | Year: 2012

Several previous studies have investigated circulating levels of the adipokine leptin in relation to gestational diabetes mellitus (GDM). However, these studies have yielded markedly conflicting results, including increased, decreased, and unchanged leptin levels in women with GDM as compared with their peers.We sought to evaluate the metabolic determinants of serum leptin in a well-characterized cohort reflecting the full spectrum of glucose intolerance in pregnancy.Metabolic characterization, including oral glucose tolerance test (OGTT) and measurement of serum leptin, insulin, lipids, adiponectin, and C-reactive protein, was performed in 817 pregnant women. The OGTT identified 198 women with GDM, 142 with gestational impaired glucose tolerance, and 477 with normal glucose tolerance.Median leptin (ng/ml) did not differ between the normal glucose tolerance (33.7), gestational impaired glucose tolerance (36.3), and GDM (36.4) groups (P = 0.085). On univariate correlation analysis, leptin was most strongly associated with prepregnancy body mass index (BMI) (r = 0.54, P < 0.0001), fasting insulin (r = 0.60, P < 0.0001), and C-reactive protein (r = 0.38, P < 0.0001) but only weakly associated with area under the glucose curve (AUC(glucose)) on the OGTT (r = 0.10, P = 0.0066). On multiple linear regression analysis, the strongest independent determinant of leptin was prepregnancy BMI (t = 11.55, P < 0.0001), whereas AUC(glucose) was not a significant predictor (t = -0.95, P = 0.34). Furthermore, although its respective associations with fasting insulin, triglycerides, and adiponectin varied across tertiles of prepregnancy BMI, leptin was not significantly associated with AUC(glucose) in any BMI tertile.Pregravid BMI, rather than gestational glucose tolerance, is the primary determinant of serum leptin concentration in pregnancy.


PubMed | Leadership Sinai Center for Diabetes
Type: Journal Article | Journal: Nutrition, metabolism, and cardiovascular diseases : NMCD | Year: 2011

Women with gestational diabetes mellitus (GDM) have an enhanced cardiovascular risk factor profile at 3-months postpartum and an elevated risk of future cardiovascular disease, as compared to their peers. Recently, it has emerged that even mild dysglycemia on antepartum oral glucose tolerance test (OGTT) predicts an increased risk of future cardiovascular disease, although it is not known whether there exists an identifiable high-risk subgroup within this patient population. Since gestational impaired glucose tolerance (GIGT) due to isolated hyperglycemia at 1-h during the OGTT (1-h GIGT) bears metabolic similarity to GDM, we hypothesized that, like GDM, 1-h GIGT may predict a high-risk postpartum cardiovascular phenotype.In this prospective cohort study, 485 women underwent antepartum OGTT, followed by cardiovascular risk factor assessment at 3-months postpartum. The antepartum OGTT identified 4 gestational glucose tolerance groups: GDM (n=137); 1-h GIGT (n=39); GIGT at 2- or 3-h (2/3-h GIGT)(n=50); and normal glucose tolerance (NGT)(n=259). After adjustment for age, ethnicity, breastfeeding and waist circumference, mean levels of the following cardiovascular risk factors progressively increased from NGT to 2/3-h GIGT to 1-h GIGT to GDM: LDL cholesterol (p=0.0026); total cholesterol:HDL (p=0.0030); apolipoprotein B (p=0.004); apolipoprotein B:apolipoprotein A1 (p=0.026); leptin (p=0.018); and C-reactive protein (p=0.011).Amongst women without GDM, 1-h GIGT predicts an enhanced postpartum cardiovascular risk factor profile. It thus emerges, that amongst young women with mild dysglycemia in pregnancy, those with 1-h GIGT may comprise an unrecognized patient population at risk for future cardiovascular disease.


PubMed | Leadership Sinai Center for Diabetes
Type: Journal Article | Journal: The Journal of clinical endocrinology and metabolism | Year: 2010

Gestational diabetes mellitus (GDM) and even mild glucose intolerance in pregnancy are both associated with increased risks of developing type 2 diabetes and cardiovascular disease in the future. Because the metabolic syndrome also identifies patients at risk of type 2 diabetes and cardiovascular disease, we hypothesized that gestational dysglycemia may be associated with an unrecognized latent metabolic syndrome. Thus, we sought to evaluate the relationship between gestational glucose tolerance status and postpartum risk of metabolic syndrome.In this prospective cohort study, 487 women underwent oral glucose tolerance testing in pregnancy and cardiometabolic characterization at 3 months postpartum. The antepartum testing defined three gestational glucose tolerance groups: GDM (n = 137); gestational impaired glucose tolerance (GIGT) (n = 91); and normal glucose tolerance (NGT) (n = 259).The primary outcome was the presence of the metabolic syndrome at 3 months postpartum, as defined by International Diabetes Federation (IDF) and American Heart Association/National Heart Lung and Blood Institute (AHA/NHLBI) criteria, respectively.The postpartum prevalence of IDF metabolic syndrome progressively increased from NGT (10.0%) to GIGT (17.6%) to GDM (20.0%) (overall P = 0.016). The same progression was observed for AHA/NHLBI metabolic syndrome (NGT, 8.9%; GIGT, 15.4%; and GDM, 16.8%; overall P = 0.046). On logistic regression analysis, both GDM (odds ratio, 2.05; 95% confidence interval, 1.07-3.94) and GIGT (odds ratio, 2.16; 95% confidence interval, 1.05-4.42) independently predicted postpartum metabolic syndrome.Both GDM and mild glucose intolerance in pregnancy predict an increased likelihood of metabolic syndrome at 3 months postpartum, supporting the concept that women with gestational dysglycemia may have an underlying latent metabolic syndrome.

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