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

IF 14.8 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes Care Pub Date : 2024-10-25 DOI:10.2337/dc24-1462

Juraj Koska, Yueming Hu, Jeremy Furtado, Dean Billheimer, Dobrin Nedelkov, Dawn Schwenke, Matthew J. Budoff, Alain G. Bertoni, Robyn L. McClelland, Peter D. Reaven

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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.

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多种族动脉粥样硬化研究》和《阿克托斯预防糖尿病研究》中血浆载脂蛋白 C-I 截短与糖尿病风险的关系

目的较高的截短-原载脂蛋白（apolipoprotein (apo) C-I proteoform）比率（C-I′/C-I）与有利的心脏代谢风险特征相关，但它们与胰岛素抵抗（IR）和糖尿病发病的纵向变化之间的关系尚不清楚。研究设计与方法通过质谱免疫测定法对多族裔动脉粥样硬化研究（MESA）中的 4,742 名非糖尿病参与者和阿克托斯预防糖尿病研究（ACT NOW）中的 524 名糖尿病前期参与者的血浆载脂蛋白 C-I 蛋白形式进行基线测量。主要结果是糖尿病发病率（MESA研究中空腹血糖[FG]≥7.0 mmol/L或服用降糖药；ACT NOW研究中空腹血糖≥7.0 mmol/L或口服葡萄糖耐量试验[OGTT]中2小时血糖≥11.1 mmol/L）。次要结果是 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 中，C-I′/C-I 越高，患糖尿病的风险越低（n = 564 例；每 SD HR 0.87 [95% CI 0.79, 0.95]；P = 0.0036；中位随访 9 年），FG 的增幅越小（随访调整基线）（-0.5%; P < 0.0001）和 HOMA-IR (-2.9%; P = 0.011)的增加幅度较小（随访调整了基线临床和人口统计学协变量，包括血浆甘油三酯和高密度脂蛋白胆固醇）。总载脂蛋白C-I浓度与FG、HOMA-IR或糖尿病发病率的变化无关。在 ACT NOW 中，C-I′/C-I 越高，AUCglucose 的升高幅度越小（-1.8%；P = 0.0052），ISI 的升高幅度越大（7.2%；P = 0.0095），糖尿病风险越低（n = 59 例；0.66 [95% CI 0.48, 0.91]；P = 0.004；中位随访 2.5 年）。结论我们的研究结果表明，apoC-I截短可能会导致血糖水平、IR和糖尿病风险的变化。

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来源期刊

Diabetes Care 医学-内分泌学与代谢

CiteScore

27.80

自引率

4.90%

发文量

449

审稿时长

1 months

期刊介绍： The journal's overarching mission can be captured by the simple word "Care," reflecting its commitment to enhancing patient well-being. Diabetes Care aims to support better patient care by addressing the comprehensive needs of healthcare professionals dedicated to managing diabetes. Diabetes Care serves as a valuable resource for healthcare practitioners, aiming to advance knowledge, foster research, and improve diabetes management. The journal publishes original research across various categories, including Clinical Care, Education, Nutrition, Psychosocial Research, Epidemiology, Health Services Research, Emerging Treatments and Technologies, Pathophysiology, Complications, and Cardiovascular and Metabolic Risk. Additionally, Diabetes Care features ADA statements, consensus reports, review articles, letters to the editor, and health/medical news, appealing to a diverse audience of physicians, researchers, psychologists, educators, and other healthcare professionals.