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肥胖的黑人与白人女性的胰岛素敏感性和骨骼肌线粒体呼吸

Insulin Sensitivity and Skeletal Muscle Mitochondrial Respiration in Black and White Women With Obesity.

作者信息

Mucinski Justine M, Distefano Giovanna, Dubé John, Toledo Frederico G S, Coen Paul M, Goodpaster Bret H, DeLany James P

机构信息

AdventHealth Orlando, Translational Research Institute, Orlando, FL 32804, USA.

School of Arts, Science, and Business, Chatham University, Pittsburgh, PA 15232, USA.

出版信息

J Clin Endocrinol Metab. 2025 May 19;110(6):e2026-e2036. doi: 10.1210/clinem/dgae600.

Abstract

OBJECTIVES

Non-Hispanic Black women (BW) have a greater risk of type 2 diabetes (T2D) and insulin resistance (IR) compared to non-Hispanic White women (WW). The mechanisms leading to these differences are not understood, and it is unclear whether synergistic effects of race and obesity impact disease risk. To understand the interaction of race and weight, hepatic and peripheral IR were compared in WW and BW with and without obesity.

METHODS

Hepatic and peripheral IR were measured by a labeled, hyperinsulinemic-euglycemic clamp in BW (n = 32) and WW (n = 32) with and without obesity. Measurements of body composition, cardiorespiratory fitness, and skeletal muscle (SM) respiration were completed. Data were analyzed by mixed model ANOVA.

RESULTS

Subjects with obesity had greater hepatic and peripheral IR and lower SM respiration (P < .001). Despite 14% greater insulin (P = .066), BW tended to have lower peripheral glucose disposal (Rd; P = .062), which was driven by women without obesity (P = .002). BW had significantly lower glucose production (P = .005), hepatic IR (P = .024), and maximal coupled and uncoupled respiration (P < .001) than WW. Maximal coupled and uncoupled SM mitochondrial respiration was strongly correlated with peripheral and hepatic IR (P < .01).

CONCLUSION

While BW without obesity had lower Rd than WW, race and obesity did not synergistically impact peripheral IR. Paradoxically, WW with obesity had greater hepatic IR compared to BW. Relationships between SM respiration and IR persisted across a range of body weights. These data provide support for therapies in BW, like exercise, that improve SM mitochondrial respiration to reduce IR and T2D risk.

摘要

目的

与非西班牙裔白人女性(WW)相比,非西班牙裔黑人女性(BW)患2型糖尿病(T2D)和胰岛素抵抗(IR)的风险更高。导致这些差异的机制尚不清楚,种族和肥胖的协同效应是否影响疾病风险也不明确。为了解种族与体重的相互作用,对有肥胖和无肥胖的WW和BW的肝脏和外周胰岛素抵抗进行了比较。

方法

通过标记的高胰岛素-正葡萄糖钳夹技术测量有肥胖和无肥胖的BW(n = 32)和WW(n = 32)的肝脏和外周胰岛素抵抗。完成身体成分、心肺适能和骨骼肌(SM)呼吸的测量。数据采用混合模型方差分析进行分析。

结果

肥胖受试者的肝脏和外周胰岛素抵抗更高,SM呼吸更低(P <.001)。尽管胰岛素水平高14%(P =.066),但BW的外周葡萄糖处置(Rd)往往较低(P =.062),这是由无肥胖的女性驱动的(P =.002)。与WW相比,BW的葡萄糖生成(P =.005)、肝脏胰岛素抵抗(P =.024)以及最大偶联和非偶联呼吸显著更低(P <.001)。最大偶联和非偶联SM线粒体呼吸与外周和肝脏胰岛素抵抗密切相关(P <.01)。

结论

虽然无肥胖的BW的Rd低于WW,但种族和肥胖并未协同影响外周胰岛素抵抗。矛盾的是,与BW相比,有肥胖的WW的肝脏胰岛素抵抗更大。SM呼吸与胰岛素抵抗之间的关系在一系列体重范围内持续存在。这些数据为针对BW的治疗方法提供了支持,如运动,可改善SM线粒体呼吸以降低胰岛素抵抗和T2D风险。

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