Department of Internal Medicine, Radboud University Medical Centre, P.O. box 9101, 6500 HB, Nijmegen, The Netherlands.
Department of Endocrinology and Nephrology, Nordsjællands Hospital, Hillerød, Denmark.
Cardiovasc Diabetol. 2024 Feb 8;23(1):55. doi: 10.1186/s12933-023-02095-w.
Hypoglycaemia has been shown to induce a systemic pro-inflammatory response, which may be driven, in part, by the adrenaline response. Prior exposure to hypoglycaemia attenuates counterregulatory hormone responses to subsequent hypoglycaemia, but whether this effect can be extrapolated to the pro-inflammatory response is unclear. Therefore, we investigated the effect of antecedent hypoglycaemia on inflammatory responses to subsequent hypoglycaemia in humans.
Healthy participants (n = 32) were recruited and randomised to two 2-h episodes of either hypoglycaemia or normoglycaemia on day 1, followed by a hyperinsulinaemic hypoglycaemic (2.8 ± 0.1 mmol/L) glucose clamp on day 2. During normoglycaemia and hypoglycaemia, and after 24 h, 72 h and 1 week, blood was drawn to determine circulating immune cell composition, phenotype and function, and 93 circulating inflammatory proteins including hs-CRP.
In the group undergoing antecedent hypoglycaemia, the adrenaline response to next-day hypoglycaemia was lower compared to the control group (1.45 ± 1.24 vs 2.68 ± 1.41 nmol/l). In both groups, day 2 hypoglycaemia increased absolute numbers of circulating immune cells, of which lymphocytes and monocytes remained elevated for the whole week. Also, the proportion of pro-inflammatory CD16-monocytes increased during hypoglycaemia. After ex vivo stimulation, monocytes released more TNF-α and IL-1β, and less IL-10 in response to hypoglycaemia, whereas levels of 19 circulating inflammatory proteins, including hs-CRP, increased for up to 1 week after the hypoglycaemic event. Most of the inflammatory responses were similar in the two groups, except the persistent pro-inflammatory protein changes were partly blunted in the group exposed to antecedent hypoglycaemia. We did not find a correlation between the adrenaline response and the inflammatory responses during hypoglycaemia.
Hypoglycaemia induces an acute and persistent pro-inflammatory response at multiple levels that occurs largely, but not completely, independent of prior exposure to hypoglycaemia. Clinical Trial information Clinicaltrials.gov no. NCT03976271 (registered 5 June 2019).
低血糖已被证明会引起全身炎症反应，这种反应部分可能是由肾上腺素反应驱动的。先前经历过低血糖会减弱对随后低血糖的代偿激素反应，但这种效应是否可以推断到炎症反应尚不清楚。因此，我们研究了先前的低血糖对人类随后低血糖时炎症反应的影响。
招募了 32 名健康参与者，并在第 1 天随机分为低血糖或正常血糖两组，每组进行 2 小时的实验，然后在第 2 天进行高胰岛素低血糖（2.8±0.1mmol/L）葡萄糖钳夹。在正常血糖和低血糖期间，以及在第 24、72 小时和 1 周后，抽取血液以确定循环免疫细胞组成、表型和功能，以及 93 种循环炎症蛋白，包括 hs-CRP。
在经历先前低血糖的组中，与对照组相比，下一天低血糖时的肾上腺素反应较低（1.45±1.24 对 2.68±1.41nmol/L）。在两组中，第 2 天的低血糖均增加了循环免疫细胞的绝对数量，其中淋巴细胞和单核细胞在整个星期内仍处于升高状态。此外，在低血糖期间，促炎 CD16-单核细胞的比例增加。在体外刺激后，单核细胞在低血糖反应中释放更多的 TNF-α和 IL-1β，而释放的 IL-10 较少，而在低血糖事件后长达 1 周内，19 种循环炎症蛋白的水平升高，包括 hs-CRP。在两组中，大多数炎症反应相似，但在暴露于先前低血糖的组中，部分持续性促炎蛋白变化减弱。我们没有发现肾上腺素反应与低血糖期间的炎症反应之间存在相关性。
低血糖在多个层面引起急性和持续性促炎反应，这些反应在很大程度上，但不完全独立于先前的低血糖暴露。临床试验信息Clinicaltrials.gov 编号：NCT03976271（注册于 2019 年 6 月 5 日）。
