TY - JOUR
T1 - Increased particle size of triacylglycerol-enriched remnant lipoproteins, but not their plasma concentration or lipid content, augments risk prediction of incident type 2 diabetes
AU - on behalf of the ELSA-Brasil study
AU - Carvalho, Luiz Sérgio F.
AU - Benseñor, Isabela M.
AU - Nogueira, Ana C.C.
AU - Duncan, Bruce B.
AU - Schmidt, Maria I.
AU - Blaha, Michael J.
AU - Toth, Peter P.
AU - Jones, Steven R.
AU - Santos, Raul D.
AU - Lotufo, Paulo A.
AU - Sposito, Andrei C.
N1 - Funding Information:
ELSA-Brasil is supported by the Brazilian Ministry of Health (Department of Science and Technology), Ministry of Science, Technology and Innovation, the National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Científico e Tecnológico [CNPq]) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Capes).This study was funded by the Brazilian Ministry of Health (Science and Technology) and the Brazilian Ministry of Science, Technology and Innovation (Financiadora de Estudos e Projetos [Finep] and CNPq). Grant numbers: 01 06 0010.00 and 01.10.0643.03 (RDS); 01 06 0212.00 and 01.10.0742-00 (BA, Brazil); 01 06 0300.00 and 01.12.0284.00 (ES, Brazil); 01 06 0278.00 and 01 10 0746 00 (MG, Brazil); 01 06 0115.00 and 01.10.0773-00 (SP, Brazil); and 01 06 0071.00 and 01.11·0093.01 (RJ, Brazil). LSFC and RDS are recipients of scholarships from the CNPq grants nos. 437413/2018-7 and 303734/2018-3, respectively. ACS is a recipient of a scholarship from the CNPq (grant no. 301465/2017-7) and the Fundação de Amparo a Pesquisa do Estado de São Paulo (Fapesp; grant no. 13/07607-8). Authors’ relationships and activities
Funding Information:
RDS has received honoraria related to consulting, research and or speaker activities from Amgen, Ach?, Astra Zeneca, Esperion, Kowa, Merck, Novo-Nordisk, PTC, Pfizer and Sanofi/Regeneron. The other authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.
Publisher Copyright:
© 2020, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2021/2
Y1 - 2021/2
N2 - Aims/hypothesis: Type 2 diabetes prevention requires the accurate identification of those at high risk. Beyond the association of fasting serum triacylglycerols with diabetes, triacylglycerol-enriched remnant lipoproteins (TRLs) more accurately reflect pathophysiological changes that underlie progression to diabetes, such as hepatic insulin resistance, pancreatic steatosis and systemic inflammation. We hypothesised that TRL-related factors could improve risk prediction for incident diabetes. Methods: We included individuals from the Brazilian Longitudinal Study of Adult Health cohort. We trained a logistic regression model for the risk of incident diabetes in 80% of the cohort using tenfold cross-validation, and tested the model in the remaining 20% of the cohort (test set). Variables included medical history and traits of the metabolic syndrome, followed by TRL-related measurements (plasma concentration, TRL particle diameter, cholesterol and triacylglycerol content). TRL features were measured using NMR spectroscopy. Discrimination was assessed using the area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC). Results: Among 4463 at-risk individuals, there were 366 new cases of diabetes after a mean (±SD) of 3.7 (±0.63) years of follow-up. We derived an 18-variable model with a global AUROC of 0.846 (95% CI: 0.829, 0.869). Overall TRL-related markers were not associated with diabetes. However, TRL particle diameter increased the AUROC, particularly in individuals with HbA1c <39 mmol/mol (5.7%) (hold-out test set [n = 659]; training-validation set [n = 2638]), but not in individuals with baseline HbA1c 39–46 mmol/mol (5.7–6.4%) (hold-out test set [n = 233]; training-validation set [n = 933]). In the subgroup with baseline HbA1c <39 mmol/mol (5.7%), AUROC in the test set increased from 0.717 (95% CI 0.603, 0.818) to 0.794 (95% CI 0.731, 0.862), and AUPRC in the test set rose from 0.582 to 0.701 when using the baseline model and the baseline model plus TRL particle diameter, respectively. TRL particle diameter was highly correlated with obesity, insulin resistance and inflammation in those with impaired fasting glucose at baseline, but less so in those with HbA1c <39 mmol/mol (5.7%). Conclusions/interpretation: TRL particle diameter improves the prediction of diabetes, but only in individuals with HbA1c <39 mmol/mol (5.7%) at baseline. These data support TRL particle diameter as a risk factor that is changed early in the course of the pathophysiological processes that lead to the development of type 2 diabetes, even before glucose abnormalities are established. [Figure not available: see fulltext.]
AB - Aims/hypothesis: Type 2 diabetes prevention requires the accurate identification of those at high risk. Beyond the association of fasting serum triacylglycerols with diabetes, triacylglycerol-enriched remnant lipoproteins (TRLs) more accurately reflect pathophysiological changes that underlie progression to diabetes, such as hepatic insulin resistance, pancreatic steatosis and systemic inflammation. We hypothesised that TRL-related factors could improve risk prediction for incident diabetes. Methods: We included individuals from the Brazilian Longitudinal Study of Adult Health cohort. We trained a logistic regression model for the risk of incident diabetes in 80% of the cohort using tenfold cross-validation, and tested the model in the remaining 20% of the cohort (test set). Variables included medical history and traits of the metabolic syndrome, followed by TRL-related measurements (plasma concentration, TRL particle diameter, cholesterol and triacylglycerol content). TRL features were measured using NMR spectroscopy. Discrimination was assessed using the area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC). Results: Among 4463 at-risk individuals, there were 366 new cases of diabetes after a mean (±SD) of 3.7 (±0.63) years of follow-up. We derived an 18-variable model with a global AUROC of 0.846 (95% CI: 0.829, 0.869). Overall TRL-related markers were not associated with diabetes. However, TRL particle diameter increased the AUROC, particularly in individuals with HbA1c <39 mmol/mol (5.7%) (hold-out test set [n = 659]; training-validation set [n = 2638]), but not in individuals with baseline HbA1c 39–46 mmol/mol (5.7–6.4%) (hold-out test set [n = 233]; training-validation set [n = 933]). In the subgroup with baseline HbA1c <39 mmol/mol (5.7%), AUROC in the test set increased from 0.717 (95% CI 0.603, 0.818) to 0.794 (95% CI 0.731, 0.862), and AUPRC in the test set rose from 0.582 to 0.701 when using the baseline model and the baseline model plus TRL particle diameter, respectively. TRL particle diameter was highly correlated with obesity, insulin resistance and inflammation in those with impaired fasting glucose at baseline, but less so in those with HbA1c <39 mmol/mol (5.7%). Conclusions/interpretation: TRL particle diameter improves the prediction of diabetes, but only in individuals with HbA1c <39 mmol/mol (5.7%) at baseline. These data support TRL particle diameter as a risk factor that is changed early in the course of the pathophysiological processes that lead to the development of type 2 diabetes, even before glucose abnormalities are established. [Figure not available: see fulltext.]
KW - Particle diameter
KW - Risk prediction
KW - Triacylglycerol-enriched remnant lipoprotein
KW - Triacylglycerol-rich lipoprotein
KW - Type 2 diabetes
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U2 - 10.1007/s00125-020-05322-1
DO - 10.1007/s00125-020-05322-1
M3 - Article
C2 - 33159534
AN - SCOPUS:85095610965
VL - 64
SP - 385
EP - 396
JO - Diabetologia
JF - Diabetologia
SN - 0012-186X
IS - 2
ER -