Fowler Lauren A, Fernández José R, O'Neil Patrick M, Parcha Vibhu, Arora Pankaj, Shetty Naman S, Cardel Michelle I, Foster Gary D, Gower Barbara A
Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA.
Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA.
Arch Med Res. 2025 Apr;56(3):103128. doi: 10.1016/j.arcmed.2024.103128. Epub 2024 Nov 22.
Type 2 diabetes (T2D) risk is higher among non-Hispanic black (NHB) and Hispanic individuals, for reasons that are unclear.
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.
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.
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]).
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.
非西班牙裔黑人（NHB）和西班牙裔个体患2型糖尿病（T2D）的风险较高，原因尚不清楚。
通过这项横断面研究，我们检验了以下假设，即T2D患病率的种族差异可部分归因于病因的异质性，这由反映不同T2D表型的基因亚型所表明。
我们使用了361名患有T2D的美国成年人的多样化样本（69.5%为女性；34.1%为NHB；13.9%为西班牙裔），从94个位点得出代表五种不同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。还使用52个单核苷酸多态性（SNP）的胰岛素抵抗（IR）风险评分评估胰岛素抵抗的遗传易感性。
与非西班牙裔白人（NHW）和西班牙裔相比，NHB参与者的β细胞和胰岛素原评分（以中位数[四分位间距]表示）更高（β细胞GRS[NHB，0.842（0.784 - 0.887）对NHW，0.762（0.702 - 0.835）和西班牙裔，0.772（0.717 - 0.848）]；胰岛素原GRS[NHB，1.006（0.973 - 1.070）对NHW，0.969（0.853 - 1.044）和西班牙裔，0.976（0.901 - 1.048）]），而NHB和西班牙裔参与者的肝脏/脂质和52 - SNP IR评分均高于NHW（肝脏/脂质GRS[NHB，1.09（0.78 - 1.18）和西班牙裔，0.895（0.736 - 1.227）对NHW，0.794（0.666 - 1.157）]；52 - SNP IR GRS[NHB，0.0095（0.009 - 0.010）和西班牙裔，0.0096（0.0092 - 0.0101）对NHW，0.0090（0.0084 - 0.0095）]）。
β细胞功能受损可能在NHB的T2D病因中起更深刻的作用，而肝功能障碍、脂质代谢异常和遗传性IR在NHB和西班牙裔中对T2D病因的贡献更大。这些发现的进一步验证可能为T2D的预防和治疗提供个性化医疗方法奠定基础。
