Jainandunsing Sjaam, Özcan Behiye, Rietveld Trinet, van Miert Joram N I, Isaacs Aaron J, Langendonk Janneke G, de Rooij Felix W M, Sijbrands Eric J G
Department of Internal Medicine, Erasmus MC - University Medical Center Rotterdam, Room Bd-299, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Acta Diabetol. 2015 Feb;52(1):11-9. doi: 10.1007/s00592-014-0588-9. Epub 2014 May 5.
We performed an extended oral glucose tolerance test (OGTT) to investigate the relationship between early and late beta-cell response and type 2 diabetes (T2D) in families of South Asian origin and indigenous Dutch, burdened by T2D. Based on the OGTT, 22 individuals were normoglycemic, 12 glucose intolerant and 23 had T2D in the South Asian families; these numbers were 34, 12 and 18 in the Caucasian families, respectively. The OGTT had 11 blood samplings in 3.5 h for glucose, insulin and C-peptide measurements. Through early and late insulin secretion rate (ISR), the above basal glucose area-under-the-curve after glucose load (glucose disposal) and insulin sensitivity index (ISI), we obtained early and late disposition indices (DI). South Asians on average had lower ISI than Caucasians (3.8 ± 2.9 vs. 6.5 ± 4.7, respectively, P < 0.001), with rapid decline of their early and late DI between normal glucose tolerance versus impaired fasting glucose/impaired glucose tolerance (late DI; P < 0.0001). Adjusted for ISI, age, gender and waist-to-hip ratio, early ISR was significantly associated with glucose disposal in South Asians (β = 0.55[0.186; 0.920]), but not in Caucasians (β = 0.09[-0.257; 0.441]). Similarly, early ISR was strongly associated with late ISR (β = 0.71[0.291; 1.123]; R (2) = 45.5 %) in South Asians, but not in Caucasians (β = 0.27[-0.035; 0.576]; R (2) = 17.4 %), with significant interaction between ethnicity and early ISR (β = 0.341[0.018; 0.664]). Ordinal regression analyses confirmed that all South Asian OGTT subgroups were homogenously resistant to insulin and solely predicted by early ISR (β = -0.782[-1.922; 0.359], β = -0.020[-0.037; -0.002], respectively), while in Caucasian families both ISI and early ISR were related to glucose tolerance state (β = -0.603[-1.105; -0.101], β = -0.066[-0.105; -0.027], respectively). In South Asian individuals, rapid beta-cell deterioration might occur under insulin resistant conditions. As their early insulin response correlates strongly with both glucose disposal and late insulin response, alterations in beta-cell dynamics may give an explanation to their extreme early onset of T2D, although larger prospective studies are required.
我们进行了一项延长口服葡萄糖耐量试验（OGTT），以研究南亚裔和荷兰本土人群中早、晚期β细胞反应与2型糖尿病（T2D）之间的关系，这些人群均受到T2D的困扰。根据OGTT结果，南亚家庭中有22人血糖正常，12人葡萄糖不耐受，23人患有T2D；在白种人家庭中，这些数字分别为34、12和18。OGTT在3.5小时内进行了11次血液采样，用于测量葡萄糖、胰岛素和C肽。通过早期和晚期胰岛素分泌率（ISR）、上述葡萄糖负荷后基础葡萄糖曲线下面积（葡萄糖处置）和胰岛素敏感性指数（ISI），我们获得了早期和晚期处置指数（DI）。南亚人的ISI平均低于白种人（分别为3.8±2.9和6.5±4.7，P<0.001），在正常糖耐量与空腹血糖受损/糖耐量受损之间，他们的早期和晚期DI迅速下降（晚期DI；P<0.0001）。在调整了ISI、年龄、性别和腰臀比后，早期ISR与南亚人的葡萄糖处置显著相关（β=0.55[0.186；0.920]），但与白种人无关（β=0.09[-0.257；0.441]）。同样，早期ISR与南亚人的晚期ISR密切相关（β=0.71[0.291；1.123]；R（2）=45.5%），但与白种人无关（β=0.27[-0.035；0.576]；R（2）=17.4%），种族与早期ISR之间存在显著交互作用（β=0.341[0.018；0.664]）。有序回归分析证实，所有南亚OGTT亚组均对胰岛素具有同等程度的抵抗，且仅由早期ISR预测（分别为β=-0.782[-1.922；0.359]，β=-0.020[-0.037；-0.002]），而在白种人家庭中，ISI和早期ISR均与糖耐量状态相关（分别为β=-0.603[-1.105；-0.101]，β=-0.066[-0.105；-0.027]）。在南亚个体中，胰岛素抵抗条件下可能会发生快速的β细胞恶化。由于他们的早期胰岛素反应与葡萄糖处置和晚期胰岛素反应均密切相关，β细胞动力学的改变可能解释了他们T2D的极早发病，尽管还需要更大规模的前瞻性研究。
