The novel inflammatory biomarker GlycA and triglyceride-rich lipoproteins are associated with the presence of subclinical myocardial dysfunction in subjects with type 1 diabetes mellitus

Puig-Jové, Carlos; Julve, Josep; Castelblanco, Esmeralda; Julián, M Teresa; Amigó, Núria; Andersen, Henrik Ullits; Ahluwalia, Tarunveer S.; Rossing, Peter; Mauricio, Daniel; Jensen, Magnus Thorsten; Alonso, Núria

doi:10.1186/s12933-022-01652-z

Cited by 10 publications

(11 citation statements)

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“…From references. 26,27 HDLc indicates high-density lipoprotein cholesterol; IDLc, intermediate-density lipoprotein cholesterol; LDLc, low-density lipoprotein cholesterol; NMR, nuclear magnetic resonance; TG, triglyceride; and VLDLc, very low-density lipoprotein cholesterol.…”

Section: Discussionmentioning

confidence: 99%

Contribution of APOE Genetic Variants to Dyslipidemia

Bea

Larrea-Sebal

Marco-Benedí

et al. 2023

ATVB

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BACKGROUND: apo (apolipoprotein) E has crucial role in lipid metabolism. The genetic variation in APOE gene is associated with monogenic disorders and contributes to polygenic hypercholesterolemia and to interindividual variability in cholesterol. APOE rare variants may be involved in the phenotype of genetic hyperlipidemias. METHODS: Exon 4 of APOE were sequenced in all consecutive unrelated subjects with primary hyperlipidemia from a Lipid Unit (n=3667) and 822 random subjects from the Aragon Workers Health Study. Binding affinity of VLDL (very low-density lipoprotein) to LDL receptor of pathogenic predicted apoE variants was analyzed in vitro. Lipoprotein particle number, size, and composition were studied by nuclear magnetic resonance. RESULTS: In addition to common polymorphisms giving rise to APOE2 and APOE4, 14 gene variants were found in exon 4 of APOE in 65 subjects. p.(Leu167del) in 8 patients with isolated hypercholesterolemia and in 8 patients with combined hyperlipidemia. Subjects with p.(Arg121Trp), p.(Gly145Asp), p.(Arg154Ser), p.(Arg163Cys), p.(Arg165Trp), and p.(Arg168His) variants met dysbetalipoproteinemia lipid criteria and were confirmed by nuclear magnetic resonance. VLDL affinity for the LDL receptor of p.(Arg163Cys) and p.(Arg165Trp) heterozygous carriers had intermedium affinity between APOE2/2 and APOE3/3. p.(Gly145Asp) and p.(Pro220Leu) variants had higher affinity than APOE3/3. CONCLUSIONS: APOE genetic variation contributes to the development of combined hyperlipidemia, usually dysbetalipoproteinemia, and familial hypercholesterolemia. The lipid phenotype in heterozygous for dysbetalipoproteinemia-associated mutations is milder than the homozygous APOE2/2-associated phenotype. Subjects with dysbetalipoproteinemia and absence of APOE2/2 are good candidates for the study of pathogenic variants in APOE . However, more investigation is required to elucidate the significance of rarer variants of apoE.

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Section: Discussionmentioning

confidence: 99%

Contribution of APOE Genetic Variants to Dyslipidemia

Bea

Larrea-Sebal

Marco-Benedí

et al. 2023

ATVB

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“…Although this study assessed LVEF in individuals with T1D, it primarily focused on subjects without known heart disease. Notably, the study only reported the mean ejection fraction (55.8 ± 7.58) [ 21 ]. The specific analysis of different phenotypes based on LVEF within the context of HF and T1D, remains insufficiently documented, presenting an area that warrants further research.…”

Section: Epidemiology Risk Factors and Prognosismentioning

confidence: 99%

“…Furthermore, a Danish cohort of T1D subjects with either diastolic or systolic subclinical myocardial dysfunction, when compared to a control group, had a longer history of diabetes (35.1 ± 14.9 vs. 30.1 ± 15.5 years; p = 0.005), a higher body mass index (BMI) (26.1 ± 3.9 vs. 25.0 ± 3.7 kg/m 2 ; p = 0.013), higher systolic blood pressure (143 vs. 136 mmHg; p < 0.001), and lower kidney function (eGFR 75.4 ± 26.2 vs. 83.7 ± 21.0 mL/min/1.73m 2 ; p = 0.003). Additionally, they were more likely to be on statin ( p = 0.039) and antihypertensive medications ( p < 0.001), and showed a higher prevalence of advanced retinopathy and albuminuria stages ( p < 0.001 for both comparisons) [ 21 ] (Table 2 ).…”

Section: Epidemiology Risk Factors and Prognosismentioning

confidence: 99%

“…Several systemic inflammatory biomarkers have been described as being associated with CVD, including HF [ 55 ]. In particular, in a study by Puig et al, the systemic pro-inflammatory molecule GlycA, a novel biomarker of protein glycan N‐acetyl groups, was associated with the presence of myocardial dysfunction in T1D subjects [ 21 ].…”

Section: Pathophysiology Of Diabetes-associated Hfmentioning

confidence: 99%

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The double burden: type 1 diabetes and heart failure—a comprehensive review

Julián,

Pérez-Montes de Oca,

Julve

et al. 2024

Cardiovasc Diabetol

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Heart failure (HF) is increasing at an alarming rate, primary due to the rising in aging, obesity and diabetes. Notably, individuals with type 1 diabetes (T1D) face a significantly elevated risk of HF, leading to more hospitalizations and increased case fatality rates. Several risk factors contribute to HF in T1D, including poor glycemic control, female gender, smoking, hypertension, elevated BMI, and albuminuria. However, early and intensive glycemic control can mitigate the long-term risk of HF in individuals with T1D. The pathophysiology of diabetes-associated HF is complex and multifactorial, and the underlying mechanisms in T1D remain incompletely elucidated. In terms of treatment, much of the evidence comes from type 2 diabetes (T2D) populations, so applying it to T1D requires caution. Sodium-glucose cotransporter 2 inhibitors have shown benefits in HF outcomes, even in non-diabetic populations. However, most of the information about HF and the evidence from cardiovascular safety trials related to glucose lowering medications refer to T2D. Glycemic control is key, but the link between hypoglycemia and HF hospitalization risk requires further study. Glycemic variability, common in T1D, is an independent HF risk factor. Technological advances offer the potential to improve glycemic control, including glycemic variability, and may play a role in preventing HF. In summary, HF in T1D is a complex challenge with unique dimensions. This review focuses on HF in individuals with T1D, exploring its epidemiology, risk factors, pathophysiology, diagnosis and treatment, which is crucial for developing tailored prevention and management strategies for this population.

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“…We have previously investigated the associations between circulating metabolites and lipid species and diabetic complications in T1D, both cross-sectionally and prospectively. [4][5][6][7][8][9] Through these studies, we have identified hydroxybutyrate isomers, ribose derivatives, and branched-chain amino acids that were associated with presence and development or progression of DR, 8 kidney disease, 5 and cardiovascular disease. 10 Similar results were also identified in relation to cardiac autonomic neuropathy.…”

Section: What This Study Addsmentioning

confidence: 99%

Circulating metabolomic markers in association with overall burden of microvascular complications in type 1 diabetes

Rotbain Curovic,

Sørland,

Hansen

et al. 2024

BMJ Open Diab Res Care

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IntroductionDiabetic retinopathy (DR), diabetic kidney disease (DKD) and distal symmetric polyneuropathy (DSPN) share common pathophysiology and pose an additive risk of early mortality.Research design and methodsIn adults with type 1 diabetes, 49 metabolites previously associated with either DR or DKD were assessed in relation to presence of DSPN. Metabolites overlapping in significance with presence of all three complications were assessed in relation to microvascular burden severity (additive number of complications—ie, presence of DKD±DR±DSPN) using linear regression models. Subsequently, the same metabolites were assessed with progression to endpoints: soft microvascular events (progression in albuminuria grade, ≥30% estimated glomerular filtration rate (eGFR) decline, or any progression in DR grade), hard microvascular events (progression to proliferative DR, chronic kidney failure, or ≥40% eGFR decline), and hard microvascular or macrovascular events (hard microvascular events, cardiovascular events (myocardial infarction, stroke, or arterial interventions), or cardiovascular mortality), using Cox models. All models were adjusted for sex, baseline age, diabetes duration, systolic blood pressure, HbA1c, body mass index, total cholesterol, smoking, and statin treatment.ResultsThe full cohort investigated consisted of 487 participants. Mean (SD) follow-up was 4.8 (2.9, 5.7) years. Baseline biothesiometry was available in 202 participants, comprising the cross-sectional cohort. Eight metabolites were significantly associated with presence of DR, DKD, and DSPN, and six with additive microvascular burden severity. In the full cohort longitudinal analysis, higher levels of 3,4-dihydroxybutanoic acid (DHBA), 2,4-DHBA, ribonic acid, glycine, and ribitol were associated with development of events in both crude and adjusted models. Adding 3,4-DHBA, ribonic acid, and glycine to a traditional risk factor model improved the discrimination of hard microvascular events.ConclusionsWhile prospective studies directly assessing the predictive ability of these markers are needed, our results strengthen the role of clinical metabolomics in relation to risk assessment of diabetic complications in chronic type 1 diabetes.

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The novel inflammatory biomarker GlycA and triglyceride-rich lipoproteins are associated with the presence of subclinical myocardial dysfunction in subjects with type 1 diabetes mellitus

Cited by 10 publications

References 50 publications

Contribution of APOE Genetic Variants to Dyslipidemia

Contribution of APOE Genetic Variants to Dyslipidemia

The double burden: type 1 diabetes and heart failure—a comprehensive review

Circulating metabolomic markers in association with overall burden of microvascular complications in type 1 diabetes

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