Dataset Information

Management of Hypertension and High Low-Density Lipoprotein in Pediatric Type 1 Diabetes.

ABSTRACT: OBJECTIVE:To evaluate hypertension and hyperlipidemia management patterns in youth with type 1 diabetes and to assess perceived effectiveness of management strategies and barriers to management. STUDY DESIGN:An electronic survey, including clinical scenarios, fielded to pediatric providers (members of the American Diabetes Association Diabetes in Youth Interest Group, Pediatric Endocrine Society, or T1D Exchange). RESULTS:Respondents (N?=?207, 86% MDs, 68% female) were practicing clinicians for youth with type 1 diabetes. As an initial recommendation, the overwhelming majority of respondents (83%-99%) endorsed lifestyle and nonmedical recommendations (eg, improve glycemic control) for hypertension and hyperlipidemia. Yet, few (6%-17%) reported these recommendations as effective. Many respondents (57%) reported referring to another specialist for hypertension, whereas few (8%) reported referring to another specialist for hyperlipidemia management. Approximately one-fifth (21%) of respondents never initiate antihypertensive medications, whereas only 8% never initiate lipid-lowering medication. Among prescribers, the majority of respondents only started antihypertensive or lipid-lowering medications after persistent elevations and in the setting of either ineffective lifestyle or nonmedical interventions or additional cardiovascular risk factors. More than two-thirds of respondents endorsed medications as often effective for hypertension and hyperlipidemia (68% and 69%, respectively). CONCLUSIONS:Pediatric diabetes providers commonly defer prescribing antihypertensive and lipid-lowering medications until nonmedication interventions have been ineffective. Most providers describe medications, but not lifestyle interventions, as often effective. Efforts to align clinical practice with clinical guidelines are needed.

SUBMITTER: Katz ML

PROVIDER: S-EPMC6013061 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Management of Hypertension and High Low-Density Lipoprotein in Pediatric Type 1 Diabetes.

Katz Michelle L ML Guo Zijing Z Laffel Lori M LM

The Journal of pediatrics 20180201

<h4>Objective</h4>To evaluate hypertension and hyperlipidemia management patterns in youth with type 1 diabetes and to assess perceived effectiveness of management strategies and barriers to management.<h4>Study design</h4>An electronic survey, including clinical scenarios, fielded to pediatric providers (members of the American Diabetes Association Diabetes in Youth Interest Group, Pediatric Endocrine Society, or T1D Exchange).<h4>Results</h4>Respondents (N = 207, 86% MDs, 68% female) were prac ...[more]

PMID: 29395184

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Project description:BackgroundMixed dyslipidemia [elevated non-high-density lipoprotein cholesterol (non-HDL-C) and triglycerides (TGs), and decreased HDL-C] is common in type 2 diabetes mellitus (T2DM) and is associated with increased cardiovascular risk. Non-HDL-C and apolipoprotein B (ApoB) are the preferred therapeutic targets for mixed dyslipidemia. Alirocumab is a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9) that effectively reduces low-density lipoprotein cholesterol (LDL-C), non-HDL-C, ApoB, and lipoprotein(a) (Lp[a]), and is well-tolerated in individuals with T2DM.MethodsThe previously reported open-label ODYSSEY DM-DYSLIPIDEMIA trial data demonstrated the effects of alirocumab on individuals with non-HDL-C ≥ 100 mg/dL and TGs ≥ 150 and < 500 mg/dL receiving stable maximally tolerated statin (n = 413). This post hoc subgroup analysis of the primary trial investigated the effects of alirocumab [75 mg every 2 weeks (Q2W) with possible increase to 150 mg Q2W at Week 12] versus usual care [ezetimibe, fenofibrate, or no additional lipid-lowering therapy (LLT)] on non-HDL-C and other lipids in individuals with T2DM and baseline TGs ≥ 200 mg/dL and HDL-C < 40 mg/dL (men) or < 50 mg/dL (women).ResultsAlirocumab significantly reduced non-HDL-C [LS mean difference (standard error (SE)), - 35.0% (3.9)], ApoB [LS mean difference (SE), - 34.7% (3.6)], LDL-C [LS mean difference (SE), - 47.3% (5.2)], LDL particle number [LS mean difference (SE), - 40.8% (4.1)], and Lp(a) [LS mean difference (SE), - 29.9% (5.4)] versus usual care from baseline to Week 24 (all P < 0.0001). Results were similar for alirocumab versus usual care. TG reductions were similar between alirocumab and usual care (no significant difference), but greater with fenofibrate versus alirocumab (P = 0.3371). Overall, alirocumab significantly increased HDL-C versus usual care [LS mean difference (SE), 7.9% (3.6); P < 0.05], although differences with alirocumab versus ezetimibe or fenofibrate were non-significant. Most individuals receiving alirocumab achieved ApoB < 80 mg/dL (67.9%) and non-HDL-C < 100 mg/dL (60.9%). Adverse event frequency was similar between alirocumab (67.2%) and usual care (70.7%). Additionally, no clinically relevant effect of alirocumab on change in glycemic parameters or use of antihyperglycemic agents was observed.ConclusionsAlirocumab is an effective therapeutic option for individuals with T2DM, TGs ≥ 200 mg/dL, and HDL-C < 40 mg/dL (men) or < 50 mg/dL (women). Atherogenic lipid (ApoB and non-HDL) reductions were greater with alirocumab than ezetimibe, fenofibrate, or no LLT. Consistent with previous studies, alirocumab was generally well tolerated. Trial registration Clinicaltrials.gov, NCT02642159. Registered December 24, 2015, https://clinicaltrials.gov/ct2/show/NCT02642159.

Project description:BackgroundIncreasing evidence showed that carbamylated lipoprotein accelerated atherosclerosis. However, whether such modification of high-density lipoprotein (HDL) particles alters in type 2 diabetes mellitus (T2DM) patients and facilitates vascular complications remains unclear. We aimed to investigate the alteration of the carbamylation in HDL among T2DM patients and clarify its potential role in atherogenesis.MethodsA total of 148 consecutive T2DM patients undergoning angiography and 40 age- and gender-matched control subjects were included. HDL was isolated from plasma samples, and the concentration of HDL carbamyl-lysine (HDL-CBL) was measured. Furthermore, the HDL from subjects and in-vitro carbamylated HDL (C-HDL) was incubated with endothelial cells and monocyte to endothelial cell adhesion. Adhesion molecule expression and signaling pathway were detected.ResultsCompared with the control group, the HDL-CBL level was remarkably increased in T2DM patients (6.13 ± 1.94 vs 12.00 ± 4.06 (ng/mg), P < 0.001). Of note, HDL-CBL demonstrated a more significant increase in T2DM patients with coronary artery disease (CAD) (n = 102) than those without CAD (n = 46) (12.75 ± 3.82 vs. 10.35 ± 4.11(ng/mg), P = 0.001). Multivariate logistic regression analysis demonstrated that higher HDL-CBL level was independently associated with a higher prevalence of CAD in diabetic patients after adjusting for established cofounders (adjusted odds ratio 1.174, 95% confidence Interval 1.045-1.319, p = 0.017). HDL from diabetic patients with CAD enhanced greater monocyte adhesion than that from the non-CAD or the control group (P < 0.001). Such pro-atherogenic capacity of diabetic HDL positively correlated with HDL-CBL level. Furthermore, in-vitro incubation of carbamylated HDL (C-HDL) with endothelial promoted monocyte to endothelial cell adhesion, induced upregulation of cell adhesion molecules expression, and activated NF-κB/p65 signaling in endothelial cells. Inhibiting carbamylation of HDL or NF-κB activation attenuated the monocyte to endothelial cell adhesion and cell surface adhesion molecules expression.ConclusionsOur study identified elevated carbamylation modification of HDL from T2DM patients, especially in those with concomitant CAD. We also evidenced that C-HDL enhanced monocyte to endothelial cell adhesion, indicating a potential pro-atherogenic role of C-HDL in atherosclerosis among T2DM patients. Trial registration https://register.clinicaltrials.gov , NCT04390711 Registered on 14 May 2020; Retrospectively registered.

Dataset Information

Management of Hypertension and High Low-Density Lipoprotein in Pediatric Type 1 Diabetes.

Publications

Management of Hypertension and High Low-Density Lipoprotein in Pediatric Type 1 Diabetes.

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