Clinical Diabetology and Metabolism, Department of Medical Sciences, Uppsala University, 751 85 Uppsala, Sweden.
J Clin Endocrinol Metab. 2024 Jan 18;109(2):e675-e688. doi: 10.1210/clinem/dgad549.
Insulin-antagonistic, counter-regulatory hormones have been implicated in the development of type 2 diabetes (T2D).
In this cross-sectional study, we investigated whether glucose-dependent regulation of such hormones differ in individuals with T2D, prediabetes (PD), and normoglycemia (NG).
Fifty-four individuals with or without T2D underwent one hyperinsulinemic-normoglycemic-hypoglycemic and one hyperglycemic clamp with repeated hormonal measurements. Participants with T2D (n = 19) were compared with a group-matched (age, sex, BMI) subset of participants without diabetes (ND, n = 17), and also with participants with PD (n = 18) and NG (n = 17).
In T2D vs ND, glucagon levels were higher and less suppressed during the hyperglycemic clamp whereas growth hormone (GH) levels were lower during hypoglycemia (P < .05). Augmented ACTH response to hypoglycemia was present in PD vs NG (P < .05), with no further elevation in T2D. In contrast, glucagon and GH alterations were more marked in T2D vs PD (P < .05).In the full cohort (n = 54), augmented responses of glucagon, cortisol, and ACTH and attenuated responses of GH correlated with adiposity, dysglycemia, and insulin resistance. In multilinear regressions, insulin resistance was the strongest predictor of elevated hypoglycemic responses of glucagon, cortisol, and ACTH. Conversely, fasting glucose and HbA1c were the strongest predictors of low GH levels during hypoglycemia and elevated, i.e. less suppressed glucagon levels during hyperglycemia, respectively. Notably, adiposity measures were also strongly associated with the responses above.
Altered counter-regulatory hormonal responses to glucose variations are observed at different stages of T2D development and may contribute to its progression by promoting insulin resistance and dysglycemia.
胰岛素拮抗、代偿性激素被认为与 2 型糖尿病（T2D）的发生有关。
在这项横断面研究中，我们研究了 T2D、前驱糖尿病（PD）和正常血糖（NG）个体中这些激素的葡萄糖依赖性调节是否存在差异。
54 名有或无 T2D 的个体接受了一次高胰岛素正常血糖低血糖和一次高血糖钳夹，并进行了多次激素测量。T2D 患者（n=19）与糖尿病（ND）患者（n=17）进行了年龄、性别、BMI 匹配的亚组比较，也与 PD（n=18）和 NG（n=17）患者进行了比较。
与 ND 相比，T2D 患者在高血糖钳夹期间胰高血糖素水平升高且抑制减少，而低血糖期间 GH 水平降低（P＜0.05）。与 NG 相比，PD 患者在低血糖期间 ACTH 反应增强（P＜0.05），而 T2D 患者则没有进一步升高。相反，与 PD 相比，T2D 患者的胰高血糖素和 GH 改变更为明显（P＜0.05）。在整个队列（n=54）中，胰高血糖素、皮质醇和 ACTH 的反应增强以及 GH 的反应减弱与肥胖、糖代谢异常和胰岛素抵抗相关。多元线性回归显示，胰岛素抵抗是低血糖期间胰高血糖素、皮质醇和 ACTH 反应增强的最强预测因子。相反，空腹血糖和 HbA1c 是低血糖期间 GH 水平降低和高血糖期间胰高血糖素水平升高（即抑制减少）的最强预测因子。值得注意的是，肥胖指标也与上述反应强烈相关。
在 T2D 发展的不同阶段，葡萄糖变化时代偿性激素的反应发生改变，可能通过促进胰岛素抵抗和糖代谢异常来促进其进展。
