Aims/hypothesis

People with isolated impaired fasting glucose (IFG) have normal beta cell function. We hypothesised that an increased glucose threshold for beta cell secretion explains IFG.

Methods

We used graded glucose infusion to examine the relationship of insulin secretion rate (ISR) and glucagon secretion rate (GSR) with rising glucose. We studied 39 non-diabetic individuals (53 ± 2 years, BMI 30 ± 1 kg/m²), categorised by fasting glucose and glucose tolerance status. After an overnight fast, a variable insulin infusion was used to maintain glucose at ~4.44 mmol/l (07:00 to 08:30 hours). At 09:00 hours, graded glucose infusion commenced at 1 mg kg⁻¹ min⁻¹ and doubled every 60 min until 13:00 hours. GSR and ISR were calculated by nonparametric deconvolution from concentrations of glucagon and C-peptide, respectively.

Results

The relationship of ISR with glucose was linear and the threshold for insulin secretion in isolated IFG did not differ from that in people with normal fasting glucose and normal glucose tolerance. GSR exhibited a single-exponential relationship with glucose that could be characterised by G₅₀, the change in glucose necessary to suppress GSR by 50%. G₅₀ was increased in IFG compared with normal fasting glucose regardless of the presence of impaired or normal glucose tolerance.

Conclusions/interpretation

These data show that, in non-diabetic humans, alpha cell dysfunction contributes to the pathogenesis of IFG independently of defects in insulin secretion. We also describe a new index that quantifies the suppression of glucagon secretion by glucose.

Graphical abstract

中文翻译：

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α和β细胞功能障碍对空腹血糖受损和葡萄糖耐量受损的不同贡献

目标/假设

孤立性空腹血糖受损 (IFG) 的人具有正常的 β 细胞功能。我们假设 β 细胞分泌的葡萄糖阈值增加可以解释 IFG。

方法

我们使用分级葡萄糖输注来检查胰岛素分泌率 (ISR) 和胰高血糖素分泌率 (GSR) 与血糖升高的关系。我们研究了 39 名非糖尿病患者（53 ± 2 岁，BMI 30 ± 1 kg/m ²），按空腹血糖和葡萄糖耐量状态分类。禁食过夜后，使用可变胰岛素输注将葡萄糖维持在 ~4.44 mmol/l（07:00 至 08:30 小时）。在 09:00 开始分级葡萄糖输注，剂量为 1 mg kg ^-1 min ^-1并且每 60 分钟加倍，直到 13:00。GSR 和 ISR 分别通过胰高血糖素和 C 肽浓度的非参数反卷积计算。

结果

ISR 与葡萄糖呈线性关系，孤立 IFG 的胰岛素分泌阈值与空腹血糖和葡萄糖耐量正常的人没有差异。GSR 表现出与葡萄糖的单指数关系，其特征在于 G ₅₀，即抑制 GSR 50% 所必需的葡萄糖变化。与正常空腹血糖相比，IFG 中的G ₅₀增加，无论是否存在葡萄糖耐量受损或正常。

结论/解释

这些数据表明，在非糖尿病人中，α 细胞功能障碍导致 IFG 的发病机制，而与胰岛素分泌缺陷无关。我们还描述了一个新指数，该指数量化葡萄糖对胰高血糖素分泌的抑制。

图形概要