Haptoglobin (Hp) binds the globin portion of free haemoglobin (Hb) thus inhibiting oxidative dama... more Haptoglobin (Hp) binds the globin portion of free haemoglobin (Hb) thus inhibiting oxidative damage: it also has anti-inflammatory and pro-angiogenic properties. There are two Hp alleles and three phenotypes, Hp 1-1, Hp 2-1, and Hp 2-2; the latter is present in ∼50% of people, and is associated with cardiovascular risk and declining renal function in diabetes patients. Preeclampsia (PE) occurs more frequently in diabetic than nondiabetic women (∼20% vs. ∼5%): reasons are not fully elucidated, but oxidative stress, inflammation, and altered angiogenesis are implicated. We determined maternal plasma Hp levels (ELISA, R and D Systems) and Hp phenotype (ELISA, Savyon Diagnostics Ltd.) in a prospective study of 23 pregnant women with type 1 diabetes (T1D) who developed PE, 24 who remained normotensive, and 19 pregnant normotensive nondiabetic women. Samples were collected at 3 visits (V1-V3) (12.4 ± 1.8, 21.7 ± 1.4, and 31.3 ± 1.4 weeks gestation (mean ± SD)). All subjects were free of microalbuminuria and hypertension at enrolment, and all visits preceded clinical PE onset. Results: Longitudinal analyses revealed significant temporal decreases of plasma Hp during pregnancy in T1D women who developed PE (p=0.001) and in nondiabetic normotensive women (p=0.017), but not in T1D who remained normotensive. Among all T1D women, plasma Hp was lower in those with Hp 2-2 vs. ’non-Hp 2-2’ phenotype at V2 (p=0.005) and V3 (p=0.002), independent of PE status. In Hp 2-2 T1D women only, plasma Hp was higher in those who did vs. did not develop PE at V1 (77.0 ± 31.4 vs. 50.7 ± 14.5 (mg/dl)) (p=0.033) and V2 (61.9 ± 19.0 vs. 42.0 ± 21.5) (p=0.046). Plasma Hp correlated positively with CRP at all visits (p<0.01), but not with previously-measured anti-angiogenic/angiogenic factors. Conclusion: Maternal plasma Hp may serve as an early marker for PE in T1D pregnancy, particularly in women with the Hp 2-2 phenotype. Disclosure C.B. Kelly: None. J. Yu: None. A. Jenkins: Research Support; Self; Medtronic, Mylan, Sanofi-Aventis. A.J. Nankervis: None. K.F. Hanssen: None. S.K. Garg: Research Support; Self; Dexcom, Inc., Eli Lilly and Company, Sanofi US. Advisory Panel; Self; Sanofi US. Research Support; Self; MannKind Corporation, Diasome Pharmaceuticals, Inc., Labstyle Innovations, Lexicon Pharmaceuticals, Inc., Medtronic. Advisory Panel; Self; Novo Nordisk A/S. C.E. Aston: None. T. Lyons: None.
Preeclampsia (PE), a major cause of maternal and fetal morbidity and mortality worldwide, has sig... more Preeclampsia (PE), a major cause of maternal and fetal morbidity and mortality worldwide, has significantly higher incidence in women with type 1 diabetes mellitus (T1DM) than in nondiabetic populations (∼20% vs. 5%, respectively). Sphingolipids are key signaling molecules, and have many roles in the structure and regulation of cellular functions. Sphingomyelin (SM) is the most abundant sphingolipid in plasma lipoproteins. There is evidence that altered SM metabolism may contribute to cardiovascular and renal complications in diabetes. We aimed to determine whether plasma concentrations of 12 SM species were associated with PE in T1DM in a prospective study of pregnancy of 23 T1DM women who developed PE and 24 T1DM who remained normotensive. Additionally, 19 normotensive nondiabetic pregnant women were included for reference. All subjects were free of microalbuminuria and hypertension at enrolment, and all visits (12, 22, 32 weeks’ gestation) preceded clinical PE onset. Results: There were no cross-sectional differences in total SM, or in any individual SM species, between diabetic women with and without PE, or between normotensive women with and without diabetes at any stage of gestation. With advancing gestation in all groups, C18-SM, C18:1-SM, C20-SM, C20:1-SM, C22-SM, C22:1-SM, C24-SM, and C24:1-SM increased (all p<0.001). LDL- and VLDL-cholesterol also increased, while HDL-cholesterol did not change. In contrast, C14-SM, C16-SM, C26-SM and C26:1-SM decreased (all p<0.001). There were no correlations between any SM species and conventional lipid profiles. Conclusions: With advancing gestation, plasma concentrations of most SM species increased, as did LDL and VLDL; however, two long-chain and two very long-chain SM species decreased. Although there were no differences in SM according to diabetes or PE status at any time point, further studies should address the significance of differential changes of SM species during pregnancy. Disclosure C.B. Kelly: None. S.M. Hammad: None. R.L. Klein: None. M.F. Lopes-Virella: None. M.J. Leyva: None. J. Yu: None. A.J. Jenkins: Advisory Panel; Self; Abbott, Australian Diabetes Society, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Mylan. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc. A.J. Nankervis: None. K.F. Hanssen: None. S.K. Garg: Advisory Panel; Self; Eli Lilly and Company, Roche Pharma, Sanofi-Aventis, Zealand Pharma A/S. Research Support; Self; Eli Lilly and Company, WebMD. J.A. Scardo: None. C.E. Aston: None. T. Lyons: None. Funding JDRF; Novo Nordisk; National Institutes of Health
The risk for preeclampsia (PE) is increased 4-fold in women with type 1 diabetes (T1D), in whom w... more The risk for preeclampsia (PE) is increased 4-fold in women with type 1 diabetes (T1D), in whom we previously demonstrated that elevated cholesterol-rich lipoproteins confer risk at the 1st trimester. Sphingolipids, including ceramides (Cer) and glycosphingolipids (hexosyl- (HexCer) and lactosyl-ceramides (LacCer)), are lipoprotein constituents that regulate cell signaling. We propose that these bio-active lipids could be modulators of PE risk. In a prospective T1D pregnancy cohort (studied at 12, 22, 32 weeks’ gestation), we used liquid chromatography/electrospray ionization-tandem mass spectrometry to determine plasma levels of 12 species of Cer, HexCer, and LacCer in 23 women with T1DM who did vs. 24 who did not develop PE, and in 19 normotensive nondiabetic pregnant women. All were free of microalbuminuria and hypertension at enrolment; all visits preceded clinical PE onset. Results: Plasma levels of C22-Cer (1st and 3rd study visits); C26:1-Cer (1st and 2nd visits); C26-Cer (1st visit); C18-Cer and C18:1-Cer (2nd visit) were significantly higher in women with T1DM who did vs. did not develop PE. C22-Cer and C26-Cer were significantly lower in T1DM vs. non-T1DM (1st visit). There were no overall PE- or diabetes-related differences in any HexCer- or LacCer species. Longitudinally, most Cer and HexCer species increased throughout pregnancy in all groups (except C14- and C18-Cer; and C14 and C26-HexCer). C16-LacCer increased, while C22:1-, C26-, and C26:1-LacCer decreased as pregnancy advanced, independent of PE status. Independent of LDL-C, total Cer increased throughout pregnancy in all groups. Conclusions: Maternal Cer species may serve as early biomarkers for PE in women with T1DM. T1DM was associated with lower levels of two Cer species. Like cholesterol-rich lipoproteins, Cer, HexCer and some LacCer species increase as pregnancy advances in all groups, but other LacCer species decrease: the significance of these findings requires further study. Disclosure C.B. Kelly: None. S.M. Hammad: None. R.L. Klein: None. M.F. Lopes-Virella: None. M.J. Leyva: None. J. Yu: None. A.J. Jenkins: Advisory Panel; Self; Abbott, Australian Diabetes Society, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Mylan. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc. A.J. Nankervis: None. K.F. Hanssen: None. S.K. Garg: Advisory Panel; Self; Eli Lilly and Company, Roche Pharma, Sanofi-Aventis, Zealand Pharma A/S. Research Support; Self; Eli Lilly and Company, WebMD. J.A. Scardo: None. C.E. Aston: None. T. Lyons: None. Funding JDRF; Novo Nordisk; National Institutes of Health
Background: Recommendations to change the diagnostic criteria for gestational diabetes mellitus (... more Background: Recommendations to change the diagnostic criteria for gestational diabetes mellitus (GDM) are controversial. Two sets of criteria are currently in use in Australia, which has led to considerable confusion. Objective: This article discusses the rationale behind the proposed changes to the diagnostic criteria, and aims to clarify the current approach to the testing for and diagnosis of GDM in Australia. Discussion: Gestational diabetes mellitus has adverse effects on pregnancy outcomes and implications for the long term wellbeing of mother and infant. New information about the relationship between hyperglycaemia in pregnancy and fetal outcomes has led to the formulation of revised recommendations for testing and diagnosis of GDM. The changes to the diagnostic threshold will increase the numbers of women diagnosed with GDM by up to 50%. Evidence that management of GDM improves neonatal outcomes mandates a proactive approach to diagnosis and management. General practitioners will have an increasing role in managing GDM.
Journal of Human Nutrition and Dietetics, Jun 6, 2023
BackgroundImmigrants worldwide have a two‐fold higher risk of gestational diabetes mellitus (GDM)... more BackgroundImmigrants worldwide have a two‐fold higher risk of gestational diabetes mellitus (GDM) than women of the host country. Providing culturally appropriate woman‐centred GDM care to attenuate adverse maternal and neonatal health outcomes is a persistent challenge for health services. Underpinned by the Knowledge to Action Framework, understanding and comparing the views of patients from different ethnic backgrounds and healthcare professionals (HCPs) about current and optimal GDM care can highlight priority areas to improve woman‐centred care. This qualitative study aimed to compare the views of ethnic Chinese and Australian‐born Caucasian women and their HCPs, including endocrinologists, obstetricians, midwives, diabetes nurse educators and dietitians, about what constitutes optimal GDM care and how to improve woman‐centred GDM care.MethodsPurposive sampling was used to recruit 42 Chinese and 30 Caucasian women with GDM and 17 HCPs from two large Australian hospital maternity services to complete in‐depth, semi‐structured interviews. Patients’ and HCPs’ views were thematically analysed and compared.ResultsFour out of nine themes showed misalignments between patients’ and HCPs’ views on GDM care, reflecting priority areas to improve woman‐centred care by (i) reaching agreement on the attitudes towards different treatment targets between HCPs; (ii) enhancing inter‐professional communication; (iii) improving GDM care transition to postpartum care; and (iv) providing detailed dietary advice tailored to Chinese patients’ cultural diet.ConclusionsFurther research on reaching consensus on treatment targets, enhancing inter‐professional communication, developing a perinatal care transition model from pregnancy to postpartum, and developing Chinese patient‐oriented educational resources is required to improve woman‐centred care.
Haptoglobin (Hp) binds the globin portion of free haemoglobin (Hb) thus inhibiting oxidative dama... more Haptoglobin (Hp) binds the globin portion of free haemoglobin (Hb) thus inhibiting oxidative damage: it also has anti-inflammatory and pro-angiogenic properties. There are two Hp alleles and three phenotypes, Hp 1-1, Hp 2-1, and Hp 2-2; the latter is present in ∼50% of people, and is associated with cardiovascular risk and declining renal function in diabetes patients. Preeclampsia (PE) occurs more frequently in diabetic than nondiabetic women (∼20% vs. ∼5%): reasons are not fully elucidated, but oxidative stress, inflammation, and altered angiogenesis are implicated. We determined maternal plasma Hp levels (ELISA, R and D Systems) and Hp phenotype (ELISA, Savyon Diagnostics Ltd.) in a prospective study of 23 pregnant women with type 1 diabetes (T1D) who developed PE, 24 who remained normotensive, and 19 pregnant normotensive nondiabetic women. Samples were collected at 3 visits (V1-V3) (12.4 ± 1.8, 21.7 ± 1.4, and 31.3 ± 1.4 weeks gestation (mean ± SD)). All subjects were free of microalbuminuria and hypertension at enrolment, and all visits preceded clinical PE onset. Results: Longitudinal analyses revealed significant temporal decreases of plasma Hp during pregnancy in T1D women who developed PE (p=0.001) and in nondiabetic normotensive women (p=0.017), but not in T1D who remained normotensive. Among all T1D women, plasma Hp was lower in those with Hp 2-2 vs. ’non-Hp 2-2’ phenotype at V2 (p=0.005) and V3 (p=0.002), independent of PE status. In Hp 2-2 T1D women only, plasma Hp was higher in those who did vs. did not develop PE at V1 (77.0 ± 31.4 vs. 50.7 ± 14.5 (mg/dl)) (p=0.033) and V2 (61.9 ± 19.0 vs. 42.0 ± 21.5) (p=0.046). Plasma Hp correlated positively with CRP at all visits (p<0.01), but not with previously-measured anti-angiogenic/angiogenic factors. Conclusion: Maternal plasma Hp may serve as an early marker for PE in T1D pregnancy, particularly in women with the Hp 2-2 phenotype. Disclosure C.B. Kelly: None. J. Yu: None. A. Jenkins: Research Support; Self; Medtronic, Mylan, Sanofi-Aventis. A.J. Nankervis: None. K.F. Hanssen: None. S.K. Garg: Research Support; Self; Dexcom, Inc., Eli Lilly and Company, Sanofi US. Advisory Panel; Self; Sanofi US. Research Support; Self; MannKind Corporation, Diasome Pharmaceuticals, Inc., Labstyle Innovations, Lexicon Pharmaceuticals, Inc., Medtronic. Advisory Panel; Self; Novo Nordisk A/S. C.E. Aston: None. T. Lyons: None.
Preeclampsia (PE), a major cause of maternal and fetal morbidity and mortality worldwide, has sig... more Preeclampsia (PE), a major cause of maternal and fetal morbidity and mortality worldwide, has significantly higher incidence in women with type 1 diabetes mellitus (T1DM) than in nondiabetic populations (∼20% vs. 5%, respectively). Sphingolipids are key signaling molecules, and have many roles in the structure and regulation of cellular functions. Sphingomyelin (SM) is the most abundant sphingolipid in plasma lipoproteins. There is evidence that altered SM metabolism may contribute to cardiovascular and renal complications in diabetes. We aimed to determine whether plasma concentrations of 12 SM species were associated with PE in T1DM in a prospective study of pregnancy of 23 T1DM women who developed PE and 24 T1DM who remained normotensive. Additionally, 19 normotensive nondiabetic pregnant women were included for reference. All subjects were free of microalbuminuria and hypertension at enrolment, and all visits (12, 22, 32 weeks’ gestation) preceded clinical PE onset. Results: There were no cross-sectional differences in total SM, or in any individual SM species, between diabetic women with and without PE, or between normotensive women with and without diabetes at any stage of gestation. With advancing gestation in all groups, C18-SM, C18:1-SM, C20-SM, C20:1-SM, C22-SM, C22:1-SM, C24-SM, and C24:1-SM increased (all p<0.001). LDL- and VLDL-cholesterol also increased, while HDL-cholesterol did not change. In contrast, C14-SM, C16-SM, C26-SM and C26:1-SM decreased (all p<0.001). There were no correlations between any SM species and conventional lipid profiles. Conclusions: With advancing gestation, plasma concentrations of most SM species increased, as did LDL and VLDL; however, two long-chain and two very long-chain SM species decreased. Although there were no differences in SM according to diabetes or PE status at any time point, further studies should address the significance of differential changes of SM species during pregnancy. Disclosure C.B. Kelly: None. S.M. Hammad: None. R.L. Klein: None. M.F. Lopes-Virella: None. M.J. Leyva: None. J. Yu: None. A.J. Jenkins: Advisory Panel; Self; Abbott, Australian Diabetes Society, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Mylan. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc. A.J. Nankervis: None. K.F. Hanssen: None. S.K. Garg: Advisory Panel; Self; Eli Lilly and Company, Roche Pharma, Sanofi-Aventis, Zealand Pharma A/S. Research Support; Self; Eli Lilly and Company, WebMD. J.A. Scardo: None. C.E. Aston: None. T. Lyons: None. Funding JDRF; Novo Nordisk; National Institutes of Health
The risk for preeclampsia (PE) is increased 4-fold in women with type 1 diabetes (T1D), in whom w... more The risk for preeclampsia (PE) is increased 4-fold in women with type 1 diabetes (T1D), in whom we previously demonstrated that elevated cholesterol-rich lipoproteins confer risk at the 1st trimester. Sphingolipids, including ceramides (Cer) and glycosphingolipids (hexosyl- (HexCer) and lactosyl-ceramides (LacCer)), are lipoprotein constituents that regulate cell signaling. We propose that these bio-active lipids could be modulators of PE risk. In a prospective T1D pregnancy cohort (studied at 12, 22, 32 weeks’ gestation), we used liquid chromatography/electrospray ionization-tandem mass spectrometry to determine plasma levels of 12 species of Cer, HexCer, and LacCer in 23 women with T1DM who did vs. 24 who did not develop PE, and in 19 normotensive nondiabetic pregnant women. All were free of microalbuminuria and hypertension at enrolment; all visits preceded clinical PE onset. Results: Plasma levels of C22-Cer (1st and 3rd study visits); C26:1-Cer (1st and 2nd visits); C26-Cer (1st visit); C18-Cer and C18:1-Cer (2nd visit) were significantly higher in women with T1DM who did vs. did not develop PE. C22-Cer and C26-Cer were significantly lower in T1DM vs. non-T1DM (1st visit). There were no overall PE- or diabetes-related differences in any HexCer- or LacCer species. Longitudinally, most Cer and HexCer species increased throughout pregnancy in all groups (except C14- and C18-Cer; and C14 and C26-HexCer). C16-LacCer increased, while C22:1-, C26-, and C26:1-LacCer decreased as pregnancy advanced, independent of PE status. Independent of LDL-C, total Cer increased throughout pregnancy in all groups. Conclusions: Maternal Cer species may serve as early biomarkers for PE in women with T1DM. T1DM was associated with lower levels of two Cer species. Like cholesterol-rich lipoproteins, Cer, HexCer and some LacCer species increase as pregnancy advances in all groups, but other LacCer species decrease: the significance of these findings requires further study. Disclosure C.B. Kelly: None. S.M. Hammad: None. R.L. Klein: None. M.F. Lopes-Virella: None. M.J. Leyva: None. J. Yu: None. A.J. Jenkins: Advisory Panel; Self; Abbott, Australian Diabetes Society, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Mylan. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc. A.J. Nankervis: None. K.F. Hanssen: None. S.K. Garg: Advisory Panel; Self; Eli Lilly and Company, Roche Pharma, Sanofi-Aventis, Zealand Pharma A/S. Research Support; Self; Eli Lilly and Company, WebMD. J.A. Scardo: None. C.E. Aston: None. T. Lyons: None. Funding JDRF; Novo Nordisk; National Institutes of Health
Background: Recommendations to change the diagnostic criteria for gestational diabetes mellitus (... more Background: Recommendations to change the diagnostic criteria for gestational diabetes mellitus (GDM) are controversial. Two sets of criteria are currently in use in Australia, which has led to considerable confusion. Objective: This article discusses the rationale behind the proposed changes to the diagnostic criteria, and aims to clarify the current approach to the testing for and diagnosis of GDM in Australia. Discussion: Gestational diabetes mellitus has adverse effects on pregnancy outcomes and implications for the long term wellbeing of mother and infant. New information about the relationship between hyperglycaemia in pregnancy and fetal outcomes has led to the formulation of revised recommendations for testing and diagnosis of GDM. The changes to the diagnostic threshold will increase the numbers of women diagnosed with GDM by up to 50%. Evidence that management of GDM improves neonatal outcomes mandates a proactive approach to diagnosis and management. General practitioners will have an increasing role in managing GDM.
Journal of Human Nutrition and Dietetics, Jun 6, 2023
BackgroundImmigrants worldwide have a two‐fold higher risk of gestational diabetes mellitus (GDM)... more BackgroundImmigrants worldwide have a two‐fold higher risk of gestational diabetes mellitus (GDM) than women of the host country. Providing culturally appropriate woman‐centred GDM care to attenuate adverse maternal and neonatal health outcomes is a persistent challenge for health services. Underpinned by the Knowledge to Action Framework, understanding and comparing the views of patients from different ethnic backgrounds and healthcare professionals (HCPs) about current and optimal GDM care can highlight priority areas to improve woman‐centred care. This qualitative study aimed to compare the views of ethnic Chinese and Australian‐born Caucasian women and their HCPs, including endocrinologists, obstetricians, midwives, diabetes nurse educators and dietitians, about what constitutes optimal GDM care and how to improve woman‐centred GDM care.MethodsPurposive sampling was used to recruit 42 Chinese and 30 Caucasian women with GDM and 17 HCPs from two large Australian hospital maternity services to complete in‐depth, semi‐structured interviews. Patients’ and HCPs’ views were thematically analysed and compared.ResultsFour out of nine themes showed misalignments between patients’ and HCPs’ views on GDM care, reflecting priority areas to improve woman‐centred care by (i) reaching agreement on the attitudes towards different treatment targets between HCPs; (ii) enhancing inter‐professional communication; (iii) improving GDM care transition to postpartum care; and (iv) providing detailed dietary advice tailored to Chinese patients’ cultural diet.ConclusionsFurther research on reaching consensus on treatment targets, enhancing inter‐professional communication, developing a perinatal care transition model from pregnancy to postpartum, and developing Chinese patient‐oriented educational resources is required to improve woman‐centred care.
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