TY - JOUR
T1 - Relationship of Plasma Apolipoprotein C-I Truncation With Risk of Diabetes in the Multi-Ethnic Study of Atherosclerosis and the Actos Now for the Prevention of Diabetes Study
AU - Koska, Juraj
AU - Hu, Yueming
AU - Furtado, Jeremy
AU - Billheimer, Dean
AU - Nedelkov, Dobrin
AU - Schwenke, Dawn
AU - Budoff, Matthew J.
AU - Bertoni, Alain G.
AU - McClelland, Robyn L.
AU - Reaven, Peter D.
N1 - Publisher Copyright:
© 2024 by the American Diabetes Association.
PY - 2024/12
Y1 - 2024/12
N2 - Higher truncated-to-native apolipoprotein (apo) C-I proteoform ratios (C-I0/C-I) are associated with favorable cardiometabolic risk profiles, but their relationship with longitudinal changes in insulin resistance (IR) and incident diabetes is unknown. RESEARCH DESIGN AND METHODS Plasma apoC-I proteoforms were measured by mass spectrometry immunoassay at baseline in 4,742 nondiabetic participants in the Multi-Ethnic Study of Atherosclerosis (MESA) and 524 participants with prediabetes in the Actos Now for Prevention of Diabetes (ACT NOW) study. The primary outcome was incident diabetes (fasting glucose [FG] $7.0mmol/L or hypoglycemicmedication use in MESA; FG$7.0mmol/L or 2-h glucose $11.1 mmol/L in an oral glucose tolerance test [OGTT] in ACT NOW). Secondary outcomes were changes in FG and HOMA-IR in MESA, and OGTT-glucose area under the curve (AUCglucose) andMatsuda insulin sensitivity index (ISI) in ACT NOW. RESULTS In MESA, a higher C-I0/C-I was associated with lower risk of diabetes (n = 564 events; HR 0.87 [95% CI 0.79, 0.95] per SD; P = 0.0036; median follow-up, 9 years), and smaller increases (follow-up adjusted for baseline) in FG (20.5%; P < 0.0001) and HOMA-IR (22.9%; P = 0.011) after adjusting for baseline clinical and demographic covariates, including plasma triglycerides and HDL cholesterol. Total apoC-I concentrations were not associated with changes in FG, HOMA-IR, or incident diabetes. In ACT NOW, higher C-I0/C-I was associated with smaller increases in AUCglucose (21.8%; P = 0.0052), greater increases in ISI (7.2%; P = 0.0095), and lower risk of diabetes (n = 59 events; 0.66 [95% CI 0.48, 0.91]; P = 0.004; median follow-up, 2.5 years) after adjusting for treatment group and diabetes risk factors, including plasma lipids. CONCLUSIONS Our results indicate that apoC-I truncation may contribute to changes in glucose levels, IR, and risk of diabetes.
AB - Higher truncated-to-native apolipoprotein (apo) C-I proteoform ratios (C-I0/C-I) are associated with favorable cardiometabolic risk profiles, but their relationship with longitudinal changes in insulin resistance (IR) and incident diabetes is unknown. RESEARCH DESIGN AND METHODS Plasma apoC-I proteoforms were measured by mass spectrometry immunoassay at baseline in 4,742 nondiabetic participants in the Multi-Ethnic Study of Atherosclerosis (MESA) and 524 participants with prediabetes in the Actos Now for Prevention of Diabetes (ACT NOW) study. The primary outcome was incident diabetes (fasting glucose [FG] $7.0mmol/L or hypoglycemicmedication use in MESA; FG$7.0mmol/L or 2-h glucose $11.1 mmol/L in an oral glucose tolerance test [OGTT] in ACT NOW). Secondary outcomes were changes in FG and HOMA-IR in MESA, and OGTT-glucose area under the curve (AUCglucose) andMatsuda insulin sensitivity index (ISI) in ACT NOW. RESULTS In MESA, a higher C-I0/C-I was associated with lower risk of diabetes (n = 564 events; HR 0.87 [95% CI 0.79, 0.95] per SD; P = 0.0036; median follow-up, 9 years), and smaller increases (follow-up adjusted for baseline) in FG (20.5%; P < 0.0001) and HOMA-IR (22.9%; P = 0.011) after adjusting for baseline clinical and demographic covariates, including plasma triglycerides and HDL cholesterol. Total apoC-I concentrations were not associated with changes in FG, HOMA-IR, or incident diabetes. In ACT NOW, higher C-I0/C-I was associated with smaller increases in AUCglucose (21.8%; P = 0.0052), greater increases in ISI (7.2%; P = 0.0095), and lower risk of diabetes (n = 59 events; 0.66 [95% CI 0.48, 0.91]; P = 0.004; median follow-up, 2.5 years) after adjusting for treatment group and diabetes risk factors, including plasma lipids. CONCLUSIONS Our results indicate that apoC-I truncation may contribute to changes in glucose levels, IR, and risk of diabetes.
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U2 - 10.2337/dc24-1462
DO - 10.2337/dc24-1462
M3 - Article
C2 - 39453822
AN - SCOPUS:85211392486
SN - 0149-5992
VL - 47
SP - 2214
EP - 2222
JO - Diabetes care
JF - Diabetes care
IS - 12
ER -