Aims/hypothesis

Postprandial hypoglycaemia (PPHG) is a frequent late complication of Roux-en-Y gastric bypass (RYGB) in people without diabetes. We aimed to examine the pathogenetic mechanisms of PPHG and its clinical consequences in people with a history of type 2 diabetes.

Methods

In this case–control study, 24 participants with type 2 diabetes treated with RYGB (14 women; median [IQR] age 53.5 [13.8] years, BMI 29.3 [6.3] kg/m², HbA_1c 36.0 [6.2] mmol/mol [5.4% (0.6%)]) underwent a dual-tracer, frequently sampled, 300 min, 75 g OGTT for the diagnosis of PPHG (glucose nadir <3.0 mmol/l, or <3.3 mmol/l with symptoms). Plasma glucose, glucose tracers, insulin, C-peptide, glucagon-like peptide-1, gastric inhibitory polypeptide, glucagon, adrenaline (epinephrine), noradrenaline (norepinephrine), cortisol and NEFAs were measured. Mathematical models were implemented to estimate glucose metabolic fluxes and beta cell function. ECG recordings, cognitive testing and hypoglycaemia awareness assessments were repeated during the OGTT. Glycaemic levels and dietary habits were assessed under free-living conditions.

Results

PPHG occurred in 12 (50%) participants, mostly without symptoms, due to excessive tracer-derived glucose clearance (mean group difference ± SE in AUC_{0–180 min} +261±72 ml min⁻¹ kg⁻¹ × min) driven by higher whole-body insulin sensitivity and early glucose-stimulated hyperinsulinaemia, the latter depending on lower insulin clearance and enhanced beta cell function, regardless of incretin hormones. PPHG participants also had defective counterregulatory hormone responses to hypoglycaemia, preventing a physiological increase in endogenous glucose production and the appearance of symptoms and signs of sympathetic cardiovascular activation and neuroglycopenia. PPHG was associated with more frequent and prolonged hypoglycaemia on 14 day continuous glucose monitoring and alterations in free-living dietary habits.

Conclusions

Our results demonstrate that post-bypass PPHG occurs frequently in individuals with a history of type 2 diabetes, often without warning symptoms, and expose its complex pathogenetic mechanisms, revealing potential therapeutic targets.

Graphical Abstract

中文翻译：

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2 型糖尿病胃旁路术后餐后低血糖：病理生理机制和临床意义

 目标/假设

餐后低血糖症 （PPHG） 是非糖尿病人群中 Roux-en-Y 胃旁路术 （RYGB） 的常见晚期并发症。我们旨在检查 PPHG 的发病机制及其对 2 型糖尿病病史患者的临床后果。

 方法

在这项病例对照研究中，24 名接受 RYGB 治疗的 2 型糖尿病参与者（14 名女性;中位 [IQR] 年龄 53.5 [13.8] 岁，BMI 29.3 [6.3] kg/m 2，HbA_1c 36.0 [6.2] mmol/mol [5.4% （0.6%）]）接受了双示踪剂，频繁采样，300 分钟，75 g OGTT 以诊断 PPHG（葡萄糖最低点 <3.0 mmol/l， 或 <3.3 mmol/l 有症状）。测定血糖、葡萄糖示踪剂、胰岛素、C 肽、胰高血糖素样肽-1、胃抑制多肽、胰高血糖素、肾上腺素 （epinephrine）、去甲肾上腺素 （norepinephrine）、皮质醇和 NEFAs。采用数学模型来估计葡萄糖代谢通量和 β 细胞功能。在 OGTT 期间重复心电图记录、认知测试和低血糖意识评估。在自由生活条件下评估血糖水平和饮食习惯。

 结果

PPHG 发生在 12 名 （50%） 参与者中，大多数没有症状，这是由于示踪剂衍生±的葡萄糖清除率（AUC_{0-180 分钟} +261±72 ml ^{min-1 kg-1} × min 的 SE 平均组差）由较高的全身胰岛素敏感性和早期葡萄糖刺激的高胰岛素血症驱动，后者取决于较低的胰岛素清除率和增强的 β 细胞功能，与肠促胰岛素激素无关。PPHG 参与者对低血糖的反调节激素反应也存在缺陷，阻止了内源性葡萄糖产生的生理性增加以及交感神经心血管激活和神经低血糖减少症的症状和体征的出现。PPHG 与 14 天连续血糖监测中更频繁和更持久的低血糖以及自由生活饮食习惯的改变相关。

 结论

我们的结果表明，旁路术后 PPHG 经常发生在有 2 型糖尿病病史的个体中，通常没有预警症状，并揭示了其复杂的发病机制，揭示了潜在的治疗靶点。

 图形摘要