Plasma levels of GlycA, a pro-inflammatory glycoprotein biomarker, associate with an increased risk of microvascular complications in patients with type 2 diabetes (Zodiac-62)

Bourgonje, Arno R.; Vaart, Amarens van der; Gruppen, Eke G.; Goor, Harry van; Bakker, Stephan J. L.; Connelly, Margery A.; Dijk, Peter R. van; Dullaart, Robin

doi:10.1007/s12020-023-03319-5

Cited by 3 publications

(2 citation statements)

References 18 publications

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“…In a prospective study of patients with established T2D who were followed up for a median of 3.2 years, 49 of 145 (33.8%) patients developed microvascular complications (i.e. nephropathy, retinopathy, or neuropathy) [ 58 ]. Whereas hsCRP was not significantly associated with incident microvascular complications, GlycA was determined to be an independent predictor in multivariable Cox regression models [ 58 ].…”

Section: Prediction Of Incident Cvdmentioning

confidence: 99%

“…nephropathy, retinopathy, or neuropathy) [ 58 ]. Whereas hsCRP was not significantly associated with incident microvascular complications, GlycA was determined to be an independent predictor in multivariable Cox regression models [ 58 ]. For each standard deviation above the mean, the risk of incident microvascular complications was increased by 79% even after adjusting for hsCRP [ 58 ].…”

Section: Prediction Of Incident Cvdmentioning

confidence: 99%

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Towards clinical application of GlycA and GlycB for early detection of inflammation associated with (pre)diabetes and cardiovascular disease: recent evidence and updates

Fung,

Chan,

et al. 2023

J Inflamm

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Summary Cardiometabolic diseases are associated with low-grade inflammation early in life and persists into old age. The long latency period presents opportunities for early detection, lifestyle modification and intervention. However, the performance of conventional biomarker assays to detect low-grade inflammation has been variable, particularly for early-stage cardiometabolic disorder including prediabetes and subclinical atherosclerotic vascular inflammation. During the last decade, the application of nuclear magnetic resonance (NMR) spectroscopy for metabolic profiling of biofluids in translational and epidemiological research has advanced to a stage approaching clinical application. Proton (1H)-NMR profiling induces no destructible physical changes to specimens, and generates quantitative signals from deconvoluted spectra that are highly repeatable and reproducible. Apart from quantitative analysis of amino acids, lipids/lipoproteins, metabolic intermediates and small proteins, 1H-NMR technology is unique in being able to detect composite signals of acute-phase and low-grade inflammation indicated by glycosylated acetyls (GlycA) and N-acetylneuraminic acid (sialic acid) moieties (GlycB). Different from conventional immunoassays that target epitopes and are susceptible to conformational variation in protein structure and binding, GlycA and GlycB signals are stable over time, and maybe complementary as well as superior to high-sensitivity C-reactive protein and other inflammatory cytokines. Here we review the physicochemical principles behind 1H-NMR profiling of GlycA and GlycB, and the available evidence supporting their potential clinical application for the prediction of incident (pre)diabetes, cardiovascular disease, and adverse outcomes.

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Section: Prediction Of Incident Cvdmentioning

confidence: 99%

Section: Prediction Of Incident Cvdmentioning

confidence: 99%

Towards clinical application of GlycA and GlycB for early detection of inflammation associated with (pre)diabetes and cardiovascular disease: recent evidence and updates

Fung,

Chan,

et al. 2023

J Inflamm

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Both LDL and HDL particle concentrations associate positively with an increased risk of developing microvascular complications in patients with type 2 diabetes: lost protection by HDL (Zodiac-63)

Bourgonje

Connelly

Goor

et al. 2023

Cardiovasc Diabetol

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Background Triglyceride-rich lipoproteins (TRL) and low-density lipoproteins (LDL) are associated positively whereas high-density lipoproteins (HDL) are associated inversely with the development of new-onset type 2 diabetes (T2D). Here we studied potential associations between these lipoprotein particle concentrations and the risk of developing microvascular complications in patients with established T2D. Methods Lipoprotein particle concentrations (TRLP, LDLP, and HDLP) were determined in 278 patients with T2D participating in a primary care-based longitudinal cohort study (Zwolle Outpatient Diabetes project Integrating Available Care [ZODIAC] study) leveraging the Vantera nuclear magnetic resonance (NMR) platform using the LP4 algorithm. Associations between lipoprotein particles and incident microvascular complications (nephropathy, neuropathy, and retinopathy) were assessed using Cox proportional hazards regression models. Results In total, 136 patients had microvascular complications at baseline. During a median follow-up of 3.2 years, 49 (34.5%) of 142 patients without microvascular complications at baseline developed new-onset microvascular complications. In multivariable Cox proportional hazards regression analyses, both total LDLP and HDLP concentrations, but not total TRLP concentrations, were positively associated with an increased risk of developing any microvascular complications after adjustment for potential confounding factors, including age, sex, disease duration, HbA1c levels, history of macrovascular complications, and statin use (adjusted hazard ratio [HR] per 1 SD increment: 1.70 [95% CI 1.24–2.34], P < 0.001 and 1.63 [95% CI 1.19–2.23], P = 0.002, respectively). When analyzing each microvascular complication individually, total LDLP concentrations were positively associated with retinopathy (adjusted HR 3.35, 95% CI 1.35–8.30, P = 0.009) and nephropathy (adjusted HR 2.13, 95% CI 1.27–3.35, P = 0.004), and total HDLP concentrations with neuropathy (adjusted HR 1.77, 95% CI 1.15–2.70, P = 0.009). No significant associations were observed for lipoprotein particle subfractions. Conclusions Total lipoprotein particle concentrations of both LDL and HDL associate positively with an increased risk of developing microvascular complications in T2D. We propose that the protective role of HDL on the development of microvascular complications may be lost in established T2D.

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Enhanced Chronic Inflammation and Increased Branched-Chain Amino Acids in Adrenal Disorders: A Cross-Sectional Study

Kittithaworn,

Dogra,

Saini

et al. 2024

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context Patients with adrenal hormone excess demonstrate increased cardiovascular risk and mortality. Objective We aimed to determine the impact of adrenal disorders on the inflammation marker GlycA, total branched-chain amino acids (BCAA), ketone bodies and the gut microbiome-derived metabolites trimethylamine N-oxide (TMAO) and betaine. Methods We conducted a single-center cross-sectional study of patients with nonfunctioning adenomas (NFA), mild autonomous cortisol secretion (MACS), primary aldosteronism (PA), Cushing syndrome (CS), pheochromocytoma/paragangliomas (PPGL), other benign or malignant adrenal masses, and adrenocortical carcinoma (ACC) between January 2015 and July 2022 (n=802). Referent subjects included participants of the PREVEND (Prevention of Renal and Vascular End-stage Disease) study (n=5241). GlycA, BCAA, ketone bodies, TMAO, and betaine were measured using nuclear magnetic resonance spectroscopy. Multivariable logistic analyses were adjusted for age, sex, BMI, smoking, hypertension, diabetes mellitus and statin therapy. Results In age-and sex-adjusted comparison to referent subjects, increased GlycA was noted in all patient categories, increased BCAA in NFA, MACS, CS, PA and ACC, increased TMAO in patients with other malignant adrenal masses, increased betaine in NFA and MACS, and increased ketone bodies in NFA, CS and ACC. Essentially similar findings were observed in fully adjusted analysis and after exclusion of subjects with diabetes and cardiovascular disease. Conclusion Patients with functioning and non-functioning adrenal masses demonstrated increased GlycA and BCAA, biomarkers associated with adverse cardiometabolic disorders and mortality. Patients with NFA demonstrated an adverse metabolic profile similar to patients with MACS and CS.

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Plasma levels of GlycA, a pro-inflammatory glycoprotein biomarker, associate with an increased risk of microvascular complications in patients with type 2 diabetes (Zodiac-62)

Abstract: Plasma levels of GlycA, a pro-inflammatory glycoprotein biomarker, associate with an increased risk of microvascular complications in patients with type 2 diabetes (Zodiac-62)

Cited by 3 publications

References 18 publications

Towards clinical application of GlycA and GlycB for early detection of inflammation associated with (pre)diabetes and cardiovascular disease: recent evidence and updates

Towards clinical application of GlycA and GlycB for early detection of inflammation associated with (pre)diabetes and cardiovascular disease: recent evidence and updates

Both LDL and HDL particle concentrations associate positively with an increased risk of developing microvascular complications in patients with type 2 diabetes: lost protection by HDL (Zodiac-63)

Enhanced Chronic Inflammation and Increased Branched-Chain Amino Acids in Adrenal Disorders: A Cross-Sectional Study

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