Division of Endocrinology, Diabetes & Metabolism, Mayo Clinic College of Medicine, Rochester, MN, USA.
Department of Information Engineering, University of Padua, Padua, Italy.
Metabolism. 2020 Apr;105:154175. doi: 10.1016/j.metabol.2020.154175. Epub 2020 Feb 8.
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.
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.
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.
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.
异常的胰高血糖素浓度是糖尿病前期的特征，但尚不确定α细胞功能障碍是否导致β细胞功能进行性下降。因此，我们试图确定β细胞功能的下降是否与餐后期间更高的胰高血糖素最低点或更高的空腹胰高血糖素有关。
这是一项纵向研究，其中 73 名非糖尿病患者在 6.6±0.3 年内两次接受 2 小时 7 样本口服葡萄糖耐量试验。使用口服最小模型应用于研究期间葡萄糖、胰岛素、C 肽浓度的测量来计算处置指数（DI）。随后，我们在调整体重变化和 DI 的基线值后，检查了基线时胰高血糖素浓度与 DI 变化（用作β细胞功能的衡量标准）之间的关系。
在调整了协变量后，餐后胰高血糖素最低点浓度与 DI 所衡量的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。
α细胞功能缺陷，表现为空腹胰高血糖素升高，与随后β细胞功能下降有关。异常的α细胞功能是否直接导致 2 型糖尿病发病机制中β细胞分泌能力丧失，仍有待确定。
