Search

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 trajectories of cardiovascular risk factors over the first 5-years after pregnancy., Methods: In this prospective observational cohort study, 330 women (mean age 35.7 ± 4.3 years, mean pre-pregnancy body mass index 25.2 ± 4.8 kg/m 2 , 50.9% primiparous) underwent serial cardiometabolic characterization (anthropometry, blood pressure, lipids, oral glucose tolerance test, insulin sensitivity/resistance (Matsuda index, HOMA-IR), C-reactive protein (CRP), adiponectin) at 1-year, 3-years, and 5-years postpartum. Based on the magnitude of weight change between pre-pregnancy and 5-years postpartum, they were stratified into the following 3 groups: weight loss (n = 100), weight gain 0-6% (n = 110), and weight gain ≥ 6% (n = 120)., Results: At 1-year postpartum, cardiovascular risk factors did not differ between the groups. However, an adverse risk factor profile progressively emerged in the weight retention groups at 3- and 5-years. Indeed, after covariate adjustment, there was stepwise worsening (from the weight loss group to weight gain 0-6% to weight gain ≥ 6% group) of the following cardiovascular risk factors at 5-years: triglycerides (p = 0.001), HDL (p = 0.02), LDL (p = 0.01), apolipoprotein-B (p = 0.003), Matsuda index (p < 0.0001), HOMA-IR (p < 0.0001), fasting glucose (p = 0.07), and CRP (p = 0.01). Moreover, on logistic regression analyses, weight gain ≥ 6% emerged as an independent predictor of pre-diabetes/diabetes at 5-years (adjusted OR = 3.40, 95%CI: 1.63-7.09)., Conclusion: Postpartum weight retention predicts trajectories of worsening cardiovascular risk factors and glucose intolerance over the first 5-years after delivery, consistent with its postulated contribution to future vascular disease in women., (© 2024. The Author(s).)

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.

Background: Indigenous populations of Australia and Canada experience disproportionately high rates of chronic disease. Our goal was to compare cardiovascular (CVD) risk profile and diabetes complications from three recent comprehensive studies of diabetes complications in different Indigenous populations in Australia and Canada., Methods: We compared participants from three recent studies: remote Indigenous Australians (2002-2003, n = 37 known diabetes), urban Indigenous Australians (2003-2005, n = 99 known diabetes), and remote Aboriginal Canadians (2001-2002, n = 188 known diabetes)., Results: The three groups were similar for HbA1c, systolic BP, diabetes duration. Although leaner by body-mass-index criteria, remote Indigenous Australians displayed a more adverse CVD risk profile with respect to: waist-hip-ratio (1.03, 0.99, 0.94, remote Indigenous Australians, urban Indigenous Australians, remote Canadians, p < 0.001); HDL-cholesterol (0.82, 0.96, 1.17 mmol/L, p < 0.001); urine albumin-creatinine-ratio (10.3, 2.4, 4.5 mg/mmol); and C-reactive protein. With respect to diabetes complications, microalbuminuria (50%, 25%, 41%, p = 0.001) was more common among both remote groups than urban Indigenous Australians, but there were no differences for peripheral neuropathy, retinopathy or peripheral vascular disease., Conclusions: Although there are many similarities in diabetes phenotype in Indigenous populations, this comparison demonstrates that CVD risk profiles and diabetes complications may differ among groups. Irrespective, management and intervention strategies are required from a young age in Indigenous populations and need to be designed in consultation with communities and tailored to community and individual needs.

Background: C-reactive protein (CRP), a biomarker of inflammation, has been associated with increased risk of developing cardiovascular disease. Common variants of the hepatocyte nuclear factor 1A (HNF1A) gene encoding HNF-1alpha have been associated with plasma CRP in predominantly European Caucasian samples. HNF1A might therefore have an impact on vascular disease and diabetes risk that is mediated by CRP. In an Aboriginal Canadian population, a private polymorphism, HNF1A G319S, was associated with increased prevalence of type 2 diabetes. However, it has not been investigated whether this association is mediated by CRP. We aimed to investigate whether CRP was mediating the association between HNF1A G319S and type 2 diabetes in an Aboriginal Canadian population with a high prevalence of diabetes., Methods: A total of 718 individuals who participated in a diabetes prevalence and risk factor survey were included in the current analysis. Participants were genotyped for HNF1A G319S. Fasting plasma samples were analyzed for CRP. Fasting plasma glucose and a 75-g oral glucose tolerance test were obtained to determine type 2 diabetes., Results: The prevalence rate of type 2 diabetes was 17.4% (125/718) using the 1999 World Health Organization definition and was higher among S319 allele carriers compared to G/G homozygotes (p < 0.0001). Among participants without type 2 diabetes, CRP levels were higher among G/G homozygotes (1.64 [95% confidence interval 1.35-2.00] mg/l) than in S319 carriers (1.26 [1.04-1.54] mg/l) (p = 0.009) after adjustment for age, sex, 2-h post-load glucose, waist circumference, and serum amyloid A. CRP levels were elevated among those with diabetes after similar adjustment (4.39 [95% confidence interval 3.09-6.23] and 4.44 [3.13-6.30] mg/L, respectively), and no significant difference in CRP was observed between S319 carriers and non-carriers (p = 0.95)., Conclusions: CRP levels were lower in S319 allele carriers of the HNF1A gene compared to non-carriers among individuals without diabetes, but this difference was not present among those with diabetes, who uniformly had elevated CRP levels. Therefore, while HNF1A appears to influence CRP concentrations in the non-diabetic state, chronic elevation of CRP is unlikely mediating the association between the HNF1A polymorphism and the high prevalence of type 2 diabetes in this Aboriginal population.

Background: The rs9939609 T>A single-nucleotide polymorphism (SNP) in the FTO gene has previously been found to be associated with obesity in European Caucasian samples. The objective of this study is to examine whether this association extends to metabolic syndrome (MetS) and applies in non-Caucasian samples., Methods: The FTO rs9939609 SNP was genotyped in 2121 subjects from four different non-Caucasian geographical ancestries. Subjects were classified for the presence or absence of MetS according to the International Diabetes Federation (IDF) and National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III definitions., Results: Carriers of > or = 1 copy of the rs9939609 A allele were significantly more likely to have IDF-defined MetS (35.8%) than non-carriers (31.2%), corresponding to a carrier odds ratio (OR) of 1.23 (95% confidence interval [CI] 1.01 to 1.50), with a similar trend for the NCEP ATP III-defined MetS. Subgroup analysis showed that the association was particularly strong in men. The association was related to a higher proportion of rs9939609 A allele carriers meeting the waist circumference criterion; a higher proportion also met the HDL cholesterol criterion compared with wild-type homozygotes., Conclusion: Thus, the FTO rs9939609 SNP was associated with an increased risk for MetS in this multi-ethnic sample, confirming that the association extends to non-Caucasian population samples.

Background: Individuals with diabetes are twice as likely to develop peripheral arterial disease (PAD), the manifestation of extensive atherosclerosis throughout the lower extremities. One putative determinant of PAD is the 677C>T polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR), which has previously been found to associate with various diabetic complications including retinopathy, nephropathy, atherosclerosis and coronary heart disease. The objective of this study was to investigate a possible role for the MTHFR 677C>T gene polymorphism with PAD in subjects with type 2 diabetes from an isolated aboriginal Canadian population., Methods: The 677C>T MTHFR gene polymorphism was genotyped in 138 subjects of Oji-Cree descent. Participants were selected from a community-wide survey that included PAD assessment by ankle-brachial index (ABI) measurement, and also intermittent claudication assessment by the Rose questionnaire., Results: MTHFR 677T allele carriers had an increased risk of PAD with an odds ratio of 3.54 (95% CI 1.01, 12.4), P = 0.049, after adjustment for age, sex, duration of diabetes, hypertension, current smoking habits, and use of insulin or oral treatment for diabetes. None of these additional co-variables was significantly associated with PAD. No association was found between MTHFR genotype and intermittent claudication., Conclusion: The genetic influence of the MTHFR 677C>T genotype on diabetic PAD is modest, yet for the Oji-Cree it is a major risk factor in comparison to other traditional risk factors.