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.

中文翻译：

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血浆载脂蛋白 C-I 截短与糖尿病风险在动脉粥样硬化多种族研究和 Actos Now 预防糖尿病研究中的关系


目的 较高的截短到天然载脂蛋白 （apo） C-I 蛋白形式比值 （C-I′/C-I） 与良好的心脏代谢风险概况相关，但它们与胰岛素抵抗 （IR） 的纵向变化和糖尿病发病的关系尚不清楚。研究设计和方法 在动脉粥样硬化多种族研究 （MESA） 中，4,742 名非糖尿病参与者和 Actos Now 预防糖尿病 （ACT NOW） 研究中 524 名糖尿病前期参与者的基线时通过质谱免疫测定法测量血浆 APOC-I 蛋白形式。主要结局是新发糖尿病 （空腹血糖 [FG] ≥7.0 mmol/L 或 MESA 中使用降糖药物;FG ≥7.0 mmol/L 或 2 小时葡萄糖≥ACT NOW 口服葡萄糖耐量试验 [OGTT] 中为 11.1 mmol/L）。次要结局是 MESA 中 FG 和 HOMA-IR 的变化，以及 ACT NOW 中 OGTT-葡萄糖曲线下面积 （AUCglucose） 和 Matsuda 胰岛素敏感性指数 （ISI） 的变化。结果 在 MESA，较高的 C-I′/C-I 与较低的糖尿病风险相关 （n = 564 个事件;HR 0.87 [95% CI 0.79， 0.95] / SD;P = 0.0036;中位随访 9 年）和 FG 的较小增加 （随访根据基线调整） （-0.5%;P < 0.0001） 和 HOMA-IR （-2.9%;P = 0.011）。总 apoC-I 浓度与 FG 、 HOMA-IR 或新发糖尿病的变化无关。在 ACT NOW 中，较高的 C-I′/C-I 与 AUCglucose 的较小增加相关 （-1.8%;P = 0.0052），ISI 增加幅度更大 （7.2%;P = 0.0095），糖尿病风险较低 （n = 59 个事件;0.66 [95% CI 0.48， 0.91];P = 0.004;中位随访 2.5 年），调整治疗组和糖尿病危险因素（包括血浆脂质）后。 结论 我们的结果表明，apoC-I 截短可能导致葡萄糖水平、IR 和糖尿病风险的变化。