ResearchPad - pregnancy-lipids-and-cv-risk—impact-of-diabetes-across-the-spectrum Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[OR08-05 Sex and Ethnic Differences in Advanced Lipoprotein Profiles in South Asians, African-Americans, and Caucasians]]> Background: African-Americans (AA) and South Asians (SA) are known to have higher risk for T2D and cardiovascular disease (CVD) compared to Caucasians (CA). Advanced analysis of lipoprotein particles with nuclear magnetic resonance (NMR) spectroscopy can offer insights into CVD risk and lipid metabolism beyond a standard lipid panel. Insulin resistance (IR) is known to be associated with atherogenic lipoprotein profile.

Objective: To characterize the lipoprotein profile in AA, CA, and SA men and women.

Design: A cross-sectional study of 182 healthy, non-diabetic SA, AA and CA patients was conducted at NIH. Subjects underwent an intravenous glucose tolerance test from which insulin sensitivity (Si) was derived using the Minimal Model. Lipoprotein profiles were measured by NMR with the LP4 deconvolution algorithm, which reports triglyceride-rich lipoprotein particles (TRLPs), high-density lipoprotein particles (HDLPs), and low-density lipoprotein particles (LDLPs). For group comparisons, Si was adjusted for age and fat free mass. Lipoprotein parameters were adjusted for age and body fat %.

Results: Fifty-nine non-diabetic SA (33 males, 26 females), 49 AA (26 males, 23 females), and 74 CA (29 males, 45 females) were included in the study. Ethnic differences in Si were observed in men (p=0.002) but not in women (p=0.43). SA men had a significantly lower Si than both AA and CA men (p=0.02). TG concentrations and TRL particle number were significantly higher in CA men and women when compared with AA. TRLP size was not different between the ethnic groups in either sex. LDL particle number and ApoB concentration was significantly higher in SA men and women compared to AA and CA. There were no ethnic or sex differences in LDL size. HDL concentration, HDL particle number, and ApoA-I levels were not different between the groups in both sexes. However, in SA, large HDL particle number and HDL particle size was significantly lower than CA. Cholesteryl ester transfer protein (CETP) activity was significantly higher in SA men, but not women, when compared with AA and CA. Ethnic differences in LDLP and L-HDLP number remained even after adjusting for Si.

Conclusions: In SA men and women, the lipoprotein phenotype (higher LDLP and lower L-HDLP) is independent of insulin sensitivity. Increased CETP activity may contribute to the lower large HDL particle number in this group. In AA, TG and TRLP number were lower as previously reported. Further investigation is needed to determine the factors mediating the atherogenic profile in SA.

<![CDATA[OR08-03 Association of Hemoglobin A1c with Early Postpartum Metabolic Syndrome in Women with Gestational Diabetes]]> <![CDATA[OR08-01 One-Step Versus Two-Step Approach for Gestational Diabetes Mellitus Screening: Comparison of Maternal and Fetal Outcomes in a Canadian Population]]> 32 weeks.Subgroup analysis of borderline GDM women (OGTT results in between IADPSG OR 1.75 and 2.0 values) were done. Group A’s borderline patients were treated as per GDM patients. Group B’s borderline patients were not considered diabetic and had normal pregnancy care. Results were adjusted for maternal age, BMI and gestational weight gain.ResultsAt interim analysis for the year 2016, a total of 6188 pregnancies, 2664 women in center A (one-step) and 3524 in center B (two-step) were included. The prevalence of GDM was 17.1% in center A (n=456) and 14.8% in center B (n=520). Both populations were comparable in terms of risk factors for LGA except for its ethnic distribution and proportion of obese women (13.1 vs 21.6%). GDM women in center B compared to center A had significant increase in rates of LGA neonates (adjusted OR (ORa) 2.1, p=0.012); neonatal hypoglycemia (ORa 2.1, p=0.0001) and neonatal intensive care unit (NICU) admission (2.1, p=0.048). Gestational hypertension’s rate was more prevalent in center B (ORa 2.1, p=0.020) and there was a non statistical trend towards increased rate of caesareans (1.6, p=0.084).Regular prenatal care for borderline women in center B (n=94) compared to GDM care in center A (n=150) resulted in increased rate of LGA babies (ORa 3.2, p=0.049). Worse maternal outcomes were identified for gestational hypertension (9.7 vs 1.3%, p=0.035) and preeclampsia (4.3 vs 0%, p=0.021) in group B vs A, respectively.ConclusionsChoosing the one-step IADPSG criteria’s for GDM screening is associated with lower rates of LGA, neonatal hypoglycemia and NICU admissions, at the expense of increased prevalence in our population. The ongoing study will include a cost-benefit evaluation to assess if improved outcomes overbalance the increased prevalence inherent to lower diagnostic criteria. ]]> <![CDATA[OR08-04 Differences in Advanced Lipoprotein Profile Between Rabson-Mendenhall Syndrome and Lipodystrophy]]> AbstractInsulin resistance (IR) is associated with metabolic dyslipidemia (high triglycerides [TG] and low HDL) and increased cardiovascular disease (CVD) risk. In obesity-associated IR, dyslipidemia is thought to be caused by increased insulin-mediated stimulation of hepatic lipogenesis, whereas IR in glucoregulatory pathways leads to hyperglycemia. This dichotomy in insulin signaling pathways is termed selective insulin resistance. Rare human conditions exist in which there is extreme, non-selective, IR impairing all insulin signaling pathways (e.g. mutations of the insulin receptor, INSR) or extreme IR affecting only selected intracellular insulin signaling pathways analogous to obesity (e.g. lipodystrophy). Lipodystrophy leads to very high TG, low HDL, and increased CVD, while INSR mutation leads to low TG and high HDL, with unknown CVD risk. We sought to further characterize the lipid phenotype and atherogenicity in these conditions in order to understand effects of different insulin signaling pathways on CVD risk.We studied 7 patients with INSR mutation (42% female; 5 homozygous; 2 heterozygous) and 21 with lipodystrophy (85% female; 5 generalized; 16 partial). Fasting lipoprotein profiles were assessed by NMR using the LP4 deconvolution algorithm. The major lipoprotein particle categories defined by this method are small, medium, and large HDL and LDL particles (HDLP and LDLP) and very small, small, medium, large, and very large TG rich lipoprotein particles (TRLP).Very small TRLP (median 189.6 [68.7, 315.0] vs 4.5 [0.00, 9.4], p=0.0001), small LDLP (mean 1425.0 ± 636.2 vs 612.8 ± 233.9, p=0.003), small HDLP (mean 14.0 ± 4.7 vs 9.0 ± 3.2, p=0.014) were more elevated in patients with lipodystrophy vs INSR mutation. This lipoprotein profile has been associated with increased atherosclerotic coronary artery disease. GlycA, a marker of inflammation was also more elevated in lipodystrophy vs INSR mutation (435.9 ± 107.2 vs 315.7 ± 74.4, p=0.01). Insulin resistance assessed by HOMA-IR was higher in patients with INSR mutation vs lipodystrophy (mean 93.5 ± 94.4 vs 15.6 ± 14.7, p=0. 00085).) Lipoprotein insulin resistance (LPIR), an index of IR based on lipoprotein particles, was lower in patients with INSR mutation (25.0 ± 19.0 vs 84.0 ± 9.0, p < 0.0001) despite their higher HOMA-IR.In conclusion, severe, selective insulin resistance in patients with lipodystrophy was associated with a more atherogenic lipoprotein particle profile and increased inflammation compared to severe, non-selective insulin resistance caused by INSR mutations. Patients with INSR mutations had a striking discrepancy between a glucose/insulin-based index of insulin resistance (HOMA-IR) and a lipid-based marker of insulin resistance (LPIR). These findings point toward a key role of selective insulin resistance in the development of an atherogenic lipid profile, which should lead to increased CVD risk. ]]> <![CDATA[OR08-02 Do OGTT-based Insulin Secretory Response Measures Approximate 1st Phase Insulin Response in Pregnant Women?]]> 120% ideal body weight). Homeostatic Model Assessment (HOMAB), Insulinogenic index (IGI), Corrected insulin response (CIR), Insulin area under the curve/Glucose area under the curve (AUCins/AUCglu), and the Stumvoll 1st Phase Estimate (Stumvoll) were calculated from insulin and glucose levels measured fasting and 30, 60, 90, 120, and 180 minutes after an oral glucose load (75 grams pre-pregnancy, 100 grams in pregnancy). Results: The best OGTT-based measure for estimation of 1st phase insulin response differed across study timepoints. In early and late pregnancy, AUCins/AUCglu had the strongest correlation with 1st phase insulin response (early: R=0.79, P<0.0001; late: R=0.69, P<0.0001), but was not associated with 1st phase insulin response pre-pregnancy (R=0.32, P=0.08). IGI had the strongest correlation with first phase insulin response pre-pregnancy (R=0.50, P=0.005) and was correlated with 1st phase insulin response in late (R=0.68, P=0.0001), but not early (R=0.36, P=0.07) pregnancy. Stumvoll was the only OGTT-based measure that was significantly correlated with 1st phase insulin response at all timepoints (pre: R=0.44, P=0.01; early: R=0.67, P=0.0001; late: R=0.67, P=0.0001). HOMAB was the weakest correlate of 1st phase insulin response, though the correlation was significant in early pregnancy (pre: R=-0.04, P=0.82; early: R=0.33, P=0.05; late: R=0.18, P=0.28). Conclusion: OGTT-based measures of insulin secretion do not have a consistent relationship with 1st phase insulin response across pre-, early, and late pregnancy. Our findings suggest that Stumvoll can be used in OGTT-based longitudinal studies of insulin secretory response that begin prior to pregnancy and span gestation. For cross-sectional studies in pregnancy, AUCins/AUCglu are the best estimates of 1st phase insulin response. ]]> <![CDATA[OR08-06 Increased Carotid Intima Media Thickness in Pediatric Type 1 Diabetes Is Associated with Disease Duration]]>