美国成人糖尿病和超重/肥胖症患者的 2 型糖尿病遗传风险表型随血统而异。

IF 4.7 3区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Archives of Medical Research Pub Date : 2024-11-22 DOI:10.1016/j.arcmed.2024.103128

Lauren A. Fowler , José R Fernández , Patrick M. O'Neil , Vibhu Parcha , Pankaj Arora , Naman S. Shetty , Michelle I. Cardel , Gary D. Foster , Barbara A Gower

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引用次数: 0

摘要

背景：2 型糖尿病（T2D）在非西班牙裔黑人（NHB）和西班牙裔个体中的风险较高，其原因尚不清楚。目的：通过这项横断面研究，我们检验了以下假设：T2D 患病率的种族差异可部分归因于病因的异质性，如反映不同 T2D 表型的遗传亚型所示：我们利用 361 名患有 T2D 的美国成年人（69.5% 为女性；34.1% 为非裔美国人；13.9% 为西班牙裔美国人）的不同样本，从 94 个基因位点得出了代表五种不同 T2D 病理生理途径的遗传风险评分（GRS）：β 细胞、胰岛素原、肥胖、脂肪营养不良和肝脏/脂质。此外，还使用 52-SNP IR 风险评分对胰岛素抵抗（IR）的遗传易感性进行了评估：β细胞和胰岛素原评分（中位数[IQR]）在 NHB 参与者中高于 NHW 和西班牙裔（β细胞 GRS [NHB，0.842(0.784-0.887) vs. NHW，0.762-0.887]）。NHW，0.762(0.702-0.835) 和西班牙裔，0.772(0.717-0.848)]）；前胰岛素 GRS（NHB，1.006[0.973-1.070] vs. NHW，0.969[0.853-1.044] 和西班牙裔，0.976[0.901-1.0.048]），而 NHB 和西班牙裔参与者的肝脏/血脂和 52-SNP IR 评分均高于 NHW（肝脏/血脂 GRS [NHB, 1.09(0.78-1.18) and Hispanic, 0.895(0.736-1.227) vs. NHW, 0.794(0.666-1.157)]); 52-SNP IR GRS (NHB, 0.0095[0.009-0.010] and Hispanic, 0.0096 [0.0092-0.0101] vs. NHW, 0.0090[0.0084-0.0095]).Conclusions：结论：β细胞功能受损可能是非黑即白人群T2D病因的更深层次原因，而非黑即白人群和西班牙裔人群的肝功能异常、脂代谢异常和遗传性IR对T2D病因的影响程度更大。对这些发现的进一步验证可为预防和治疗 T2D 的个性化医学方法奠定基础。

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Genetic Risk Phenotypes for Type 2 Diabetes Differ with Ancestry in US Adults with Diabetes and Overweight/Obesity

Background

Type 2 diabetes (T2D) risk is higher among non-Hispanic black (NHB) and Hispanic individuals, for reasons that are unclear.

Aims

With this cross-sectional study, we tested the hypothesis that racial disparities in T2D prevalence can be partially traced to heterogeneity in etiology, as indicated by genetic subtypes that reflect distinct T2D phenotypes.

Methods

Using a diverse sample of 361 US adults with T2D (69.5% women; 34.1% NHB; 13.9% Hispanic), we derived genetic risk scores (GRS) representing five distinct T2D pathophysiological pathways from 94 loci: β-cell, proinsulin, obesity, lipodystrophy, and liver/lipid. Genetic predisposition for insulin resistance (IR) was also assessed using a 52-SNP IR risk score.

Results

The β-cell and proinsulin scores (as median [IQR]) were higher among NHB participants relative to NHW and Hispanics (β-cell GRS [NHB, 0.842(0.784–0.887) vs. NHW, 0.762(0.702–0.835) and Hispanic, 0.772(0.717–0.848)]); proinsulin GRS (NHB, 1.006[0.973–1.070] vs. NHW, 0.969[0.853–1.044] and Hispanic, 0.976[0.901–1.048]), whereas the liver/lipid and 52-SNP IR scores were higher in both NHB and Hispanic participants versus NHW (liver/lipid GRS [NHB, 1.09(0.78–1.18) and Hispanic, 0.895(0.736–1.227) vs. NHW, 0.794(0.666–1.157)]); 52-SNP IR GRS (NHB, 0.0095[0.009–0.010] and Hispanic, 0.0096 [0.0092–0.0101] vs. NHW, 0.0090[0.0084–0.0095]).

Conclusions

Impaired β-cell function may underlie T2D etiology more profoundly in NHB, whereas hepatic dysfunction, lipid metabolism abnormalities, and genetic IR contribute to T2D etiology to a greater degree in both NHB and Hispanics. Further validation of these findings may form the basis for a personalized medicine approach to prevention and treatment of T2D.

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来源期刊

Archives of Medical Research 医学-医学：研究与实验

CiteScore

12.50

自引率

0.00%

发文量

审稿时长

28 days

期刊介绍： Archives of Medical Research serves as a platform for publishing original peer-reviewed medical research, aiming to bridge gaps created by medical specialization. The journal covers three main categories - biomedical, clinical, and epidemiological contributions, along with review articles and preliminary communications. With an international scope, it presents the study of diseases from diverse perspectives, offering the medical community original investigations ranging from molecular biology to clinical epidemiology in a single publication.