Free fatty acid-mediated impairment of glucose-stimulated insulin secretion in nondiabetic Oji-Cree individuals from the Sandy Lake community of Ontario, Canada - A population at very high risk for developing type 2 diabetes
Free fatty acid-mediated impairment of glucose-stimulated insulin secretion in nondiabetic Oji-Cree individuals from the Sandy Lake community of Ontario, Canada - A population at very high risk for developing type 2 diabetes
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DOI：
10.2337/diabetes.52.6.1485
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发表时间：
2003-06-01
期刊：
影响因子：
7.7
通讯作者：
Lewis, GF
中科院分区：
文献类型：
--
作者：
Carpentier, A;Zinman, B;Lewis, GF
加拿大安大略省沙湖地区的Oji-Cree人群是世界上2型糖尿病患病率第三高的人群。在过去的半个世纪里，他们的饮食和身体活动的变化，特别是饮食中脂肪消费的显著增加，被认为是造成这种流行病的重要因素。本研究的目的是在Sandy Lake Oji-Cree人群（n = 12）中检测β细胞对48小时血浆游离脂肪酸（FFAs）大约两倍升高（由脂质内和肝素输注诱导）的反应，并将其与健康年龄匹配的非糖尿病高加索受试者（n = 16）的反应进行比较。胰岛素分泌率，胰岛素敏感性指数（SI）和处置指数（D-I）（考虑到环境SI的胰岛素分泌指数）在4小时分级静脉滴注葡萄糖和20 mmol/l 2小时高血糖钳的反应中进行评估。白种人在FFA升高48小时后对分级葡萄糖输注的总胰岛素分泌反应与生理盐水对照组相比没有变化，Oji-Cree个体增加了近30%（两组差异P = 0.04）。在两组中，输注肝素-脂内可使SI降低40% （P = 0.002）。尽管在白种人中，肝素-脂质内输注能显著降低DI（降幅接近40%），但在Oji-Cree个体中，DI仅降低了15%（两组反应差异P = 0.03）。然而，Oji-Cree个体的SI和DI在基线时已经远远低于白种人，这与该人群中2型糖尿病的高风险保持一致。由此得出结论，来自2型糖尿病高危人群的Oji-Cree人并不比健康的非native人更容易受到ffa诱导的葡萄糖刺激胰岛素分泌脱敏的影响，事实上，似乎更不容易受到ffa的影响。这是否反映了对脂肪毒性的固有抵抗或在该人群中已经存在的脂肪毒性作用，将需要进一步研究。糖尿病杂志，2003。
The Oji-Cree population of the Sandy Lake region of Ontario, Canada, has the third highest prevalence of type 2 diabetes in the world. Changes in their diet and physical activity over the past half-century, particularly the marked increase in consumption of dietary fats, are felt to be important factors accounting for this epidemic. The aim of the present study was to examine the beta-cell response to a 48-h approximately twofold elevation of plasma free fatty acids (FFAs) (induced by Intralipid and heparin infusion) in members of the Sandy Lake Oji-Cree population (n = 12) and to compare the response to that in healthy age-matched nondiabetic Caucasian subjects (n = 16). The insulin secretion rate, insulin sensitivity index (SI), and disposition index (D-I) (an index of insulin secretion that takes into account the ambient SI) were assessed in response to a 4-h graded intravenous glucose infusion followed by a 20 mmol/l 2-h hyperglycemic clamp. Total insulin secretory response to the graded glucose infusion did not change after a 48-h FFA elevation versus saline control in Caucasians and increased by similar to30% in Oji-Cree individuals (P = 0.04 for difference between the two groups). Infusion of heparin-Intralipid reduced SI by similar to40% in both groups (P = 0.002). Although DI was markedly reduced by heparin-Intralipid infusion in Caucasians (by similar to40%), it was reduced by only 15% in Oji-Cree individuals (P = 0.03 for difference of response between the two groups). However, SI and DI in the Oji-Cree individuals were already much lower than in Caucasians at baseline, in keeping with the very high risk of type 2 diabetes in this population. It is concluded that Oji-Cree individuals from a community at very high risk for developing type 2 diabetes are not more susceptible to the FFA-induced desensitization of glucose-stimulated insulin secretion than healthy non-Natives and, in fact, appear to be less susceptible. Whether this reflects an inherent resistance to lipotoxicity or an already-present lipotoxic effect in this population will require further study. Diabetes 52:1485-1495, 2003.