Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study.
Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study.
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DOI：
10.1016/s0140-6736(09)60619-x
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发表时间：
2009-06-27
期刊：
影响因子：
168.9
通讯作者：
Witte, Daniel R.
中科院分区：
文献类型：
--
作者：
Tabak, Adam G.;Jokela, Markus;Akbaraly, Tasnime N.;Brunner, Eric J.;Kivimaki, Mika;Witte, Daniel R.
人们对2型糖尿病发生前糖代谢变化的时间知之甚少。我们的目标是描述2型糖尿病患者的空腹和负荷后血糖、胰岛素敏感性和胰岛素分泌的轨迹。对6538名(70.7%男性，91.3%高加索人)无糖尿病的英国公务员进行的前瞻性职业队列研究。在中位数为8.2年的随访中，505例糖尿病患者被诊断为糖尿病(49.1%基于口服葡萄糖耐量试验)。测定空腹和负荷后2小时血糖、稳态模型评估(HOMA)胰岛素敏感性和β细胞功能直至糖尿病诊断(糖尿病组)或随访结束(非糖尿病对照组)的轨迹。根据年龄、性别和种族调整的多水平模型证实，除了胰岛素分泌在随访期间没有变化外，所有代谢指标在对照组中都遵循线性趋势。在糖尿病组中，空腹血糖线性上升之后，从糖尿病诊断前3年开始，血糖呈二次曲线急剧上升。对于负荷后2小时血糖水平，在诊断前3年开始快速升高，而对于HOMA胰岛素敏感性，在诊断之前的最后5年中出现了更急剧的下降。HOMAβ细胞功能在确诊前4至3年间呈上升趋势，之后下降至确诊前。在这一大群英国成年人中，血糖水平、胰岛素敏感性和胰岛素分泌的变化在糖尿病诊断前3-6年就已经很明显了。
Little is known about the timing of changes in glucose metabolism prior to type 2 diabetes development. We aimed to characterize trajectories of fasting and postload glucose, insulin sensitivity and insulin secretion in individuals developing type 2 diabetes. Prospective occupational cohort study of 6538 (70.7% male, 91.3% Caucasian) British civil servants free of diabetes mellitus at baseline. During a median follow-up of 8.2 years, 505 incident diabetes cases were diagnosed (49.1% based on oral glucose tolerance test). Trajectories of fasting and 2-hour postload glucose, homeostasis model assessment (HOMA) insulin sensitivity, and β-cell function until diabetes diagnosis (the diabetic group) or the end of follow-up (the non-diabetic controls) were determined. Multilevel models adjusted for age, sex and ethnicity confirmed that all metabolic measures followed linear trends in the controls except for insulin secretion that did not change during the follow-up. In the diabetic group a linear increase in fasting glucose was followed by a steep quadratic increase starting 3 years prior to the diagnosis of diabetes. For 2-hour postload glucose levels a fast elevation started 3 years prior to the diagnosis and for HOMA insulin sensitivity a steeper decrease was seen during the last 5 years before the diagnosis. HOMA β-cell function showed an increase between years 4 and 3 prior to the diagnosis and then a decrease until the diagnosis. In this large cohort of British adults changes in glucose levels, insulin sensitivity, and insulin secretion were evident already 3–6 years before the diabetes diagnosis.