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
Year: 2024
Type: article
Abstract: OBJECTIVE: Higher truncated-to-native apolipoprotein (apo) C-I proteoform ratios (C-I'/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] ≥7.0 mmol/L or hypoglycemic medication use in MESA; FG ≥7.0 mmol/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) and Matsuda insulin sensitivity index (ISI) in ACT NOW. RESULTS: In MESA, a higher C-I'/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 (-0.5%; P < 0.0001) and HOMA-IR (-2.9%; 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-I'/C-I was associated with smaller increases in AUCglucose (-1.8%; 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.
Source: Diabetes Care
DOI: 10.2337/dc24-1462
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G1261793039, MESA, G1269631540, G1276754516, G1294553593, G1311053909, G1409423729, G1412221515, G1539384734, G1640378483, G1686417863, G1803853571, G1983464145, G2095942735, G2144938473, G22458031, G2262782284, G2295196357, MESA, G2580996367, G2726417417, MESA, G2837638605, G290884426, G291913881, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--EBCT READING, G3093995152, G3570589137, G3595232572, G3647016462, G3687594596, G370977179, MESA, G3990748671, G399481048, G4086764833, G4268424353, TITLE: MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS (MESA), G4309390892, G4512137732, G4563812999, OPTION 3. 4/1/2014 - 3/31/2015. MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS (MESA) - READING CENTER, NHLBI, MESA, G4986157935, G5075046117, G5088122703, G5108002584, G514410172, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY-ULTRASOUND, G5653954166, G5654179670, G5787256936, G6095866717, G6359107525, Institute for Clinical and Translational Research, MESA, G6514094751, G66341962, G6798586005, G6856766826, Team Approach to Translate Novel Biomarkers for Diabetes, G7166352866, MESA, G7462069030, G78770644, Clinical and Translational Science Award, G8145863542, G842756795, G8761005068, G8852914737, G9000004549, G9000004784, G9000006353, G9000017360, G9000019818, G9000025517, G9000038858, G9000063950, G9000065698, G9000281817, G9000347798, G94668252, G954405230, G991334795
OpenAlex ID: W4403750185