PURPOSE Abnormal glucagon concentrations are a feature of prediabetes but it is uncertain if α-cell dysfunction contributes to a longitudinal decline in β-cell function. We therefore sought to determine if a decline in β-cell function is associated with a higher nadir glucagon in the postprandial period or with higher fasting glucagon. METHODS This was a longitudinal study in which 73 non-diabetic subjects were studied on 2 occasions 6.6 ± 0.3 years apart using a 2-hour, 7-sample oral glucose tolerance test. Disposition Index (DI) was calculated using the oral minimal model applied to the measurements of glucose, insulin, C-peptide concentrations during the studies. We subsequently examined the relationship of glucagon concentrations at baseline with change in DI (used as a measure of β-cell function) after adjusting for changes in weight and the baseline value of DI. RESULTS After adjusting for covariates, nadir postprandial glucagon concentrations were not associated with changes in β-cell function as quantified by DI. On the other hand, fasting glucagon concentrations during the baseline study were inversely correlated with longitudinal changes in DI. CONCLUSIONS Defects in α-cell function, manifest as elevated fasting glucagon, are associated with a subsequent decline in β-cell function. It remains to be ascertained if abnormal α-cell function contributes directly to loss of β-cell secretory capacity in the pathogenesis of type 2 diabetes.

中文翻译：

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在非糖尿病人群中，空腹胰高血糖素浓度与 β 细胞功能的纵向下降有关。


目的 胰高血糖素浓度异常是糖尿病前期的一个特征，但尚不确定 α 细胞功能障碍是否会导致 β 细胞功能纵向下降。因此，我们试图确定β细胞功能的下降是否与餐后较高的最低胰高血糖素或较高的空腹胰高血糖素有关。方法 这是一项纵向研究，对 73 名非糖尿病受试者进行了 2 次研究，每次相隔 6.6 ± 0.3 年，使用 2 小时、7 个样本的口服葡萄糖耐量试验。处置指数（DI）是使用口服最小模型计算的，该模型应用于研究期间的葡萄糖、胰岛素、C肽浓度的测量。在调整体重和 DI 基线值的变化后，我们随后检查了基线胰高血糖素浓度与 DI 变化（用作 β 细胞功能的测量）的关系。结果调整协变量后，餐后胰高血糖素浓度最低点与 DI 量化的 β 细胞功能变化无关。另一方面，基线研究期间的空腹胰高血糖素浓度与 DI 的纵向变化呈负相关。结论 α 细胞功能缺陷（表现为空腹胰高血糖素升高）与随后的 β 细胞功能下降有关。在 2 型糖尿病的发病机制中，α 细胞功能异常是否直接导致 β 细胞分泌能力丧失仍有待确定。