Mohandas Cynthia, Bonadonna Riccardo, Shojee-Moradie Fariba, Jackson Nicola, Boselli Linda, Alberti K George M M, Peacock Janet L, Umpleby A Margot, Amiel Stephanie A, Goff Louise M
Division of Diabetes and Nutritional Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.
Department of Medicine and Surgery, University of Parma and Azienda Ospedaliera Universitaria di Parma, Parma, Italy.
Diabetes Obes Metab. 2018 Jul;20(7):1678-1687. doi: 10.1111/dom.13283. Epub 2018 Apr 14.
To test the hypothesis that men of black (West) African ethnicity (black African men [BAM]) with early type 2 diabetes (T2D) would have greater insulin secretory deficits compared with white European men (WEM), following prediabetic hypersecretion.
In 19 BAM and 15 WEM, matched for age, body mass index and duration of diabetes, we assessed and modelled insulin secretory responses to hyperglycaemia stimulated intravenously (hyperglycaemic clamp) and orally (meal tolerance test).
With similar post-challenge glucose responses, BAM had lower second-phase C-peptide responses to intravenous glucose (BAM 70.6 vs WEM 115.1 nmol/L/min [ratio of geometric mean 0.55, 95% confidence interval {CI} 0.37, 0.83]; P = .006) and to oral glucose (BAM 65.4 vs WEM 88.5 nmol/L/min [mean difference -23.2, 95% CI -40.0, -6.3]; P = .009). Peripheral insulin response in BAM to oral glucose was preserved (BAM 47.4 vs WEM 59.4 nmol/L/min [ratio of geometric mean 0.89, 95% CI 0.59, 1.35]; P = .566), with relative reductions in insulin clearance (BAM 506.2 vs WEM 630.1 mL/m BSA/min [mean difference -123.9, 95% CI -270.5, 22.6]; P = .095), associated with enhanced incretin responses (gastric inhibitory polypeptide incremental area under the curve: BAM 46.8 vs WEM 33.9 μg/L/min [mean difference 12.9, 95% CI 2.1, 23.7]; P = .021).
In early T2D, BAM had significantly lower insulin secretory responses to intravenous and oral stimulation than WEM. Lower insulin clearance, potentially driven by increased incretin responses, may act to preserve peripheral insulin concentrations. Tailoring early management strategies to reflect distinct ethnic-specific pathophysiology may improve outcomes in this high-risk population.
验证以下假设,即患有早期2型糖尿病(T2D)的西非裔黑人男性(黑人非洲男性[BAM])与白人欧洲男性(WEM)相比,在糖尿病前期高分泌后胰岛素分泌缺陷会更严重。
选取19名BAM和15名WEM,匹配年龄、体重指数和糖尿病病程,评估并模拟静脉注射(高血糖钳夹)和口服(糖耐量试验)高血糖刺激后的胰岛素分泌反应。
在挑战后血糖反应相似的情况下,BAM对静脉注射葡萄糖的第二阶段C肽反应较低(BAM为70.6 vs WEM为115.1 nmol/L/分钟[几何平均比0.55,95%置信区间{CI} 0.37,0.83];P = 0.006),对口服葡萄糖的反应也较低(BAM为65.4 vs WEM为88.5 nmol/L/分钟[平均差异 -23.2,95% CI -40.0,-6.3];P = 0.009)。BAM对口服葡萄糖的外周胰岛素反应得以保留(BAM为47.4 vs WEM为59.4 nmol/L/分钟[几何平均比0.89,95% CI 0.59,1.35];P = 0.566),胰岛素清除率相对降低(BAM为506.2 vs WEM为630.1 mL/m体表面积/分钟[平均差异 -123.9,95% CI -270.5,22.6];P = 0.095),同时肠促胰岛素反应增强(曲线下胃抑制多肽增量面积:BAM为46.8 vs WEM为33.9 μg/L/分钟[平均差异12.9,95% CI 2.1,23.7];P = 0.021)。
在早期T2D中,BAM对静脉和口服刺激的胰岛素分泌反应显著低于WEM。胰岛素清除率降低,可能由肠促胰岛素反应增加所致,可能有助于维持外周胰岛素浓度。制定早期管理策略以反映不同种族特异性病理生理学特征,可能改善这一高危人群的治疗效果。