Gregory Justin M, Smith T Jordan, Duffus Sara H, Brooks David, Akbar M Naweed, Huntley Margaret-Anne, Gottlieb JoAnn A, LeStourgeon Lauren M, Wilson Christopher S, Beckman Joshua A, Cherrington Alan D
Ian Burr Division of Pediatric Endocrinology and Diabetes, Vanderbilt University School of Medicine, 1500 21st Avenue South, Suite 1514, Nashville, TN, 37212-3157, USA.
Division of Pediatric Endocrinology, University of North Carolina, 127 Medical School Wing E, CB# 7039, Chapel Hill, NC, 27599-7039, USA.
Cardiovasc Diabetol. 2025 Mar 5;24(1):107. doi: 10.1186/s12933-025-02658-z.
Iatrogenic peripheral hyperinsulinemia, resulting from peripheral insulin administration in type 1 diabetes, may increase insulin resistance and impair endothelial function. We hypothesized that lowering iatrogenic peripheral hyperinsulinemia via a one-week, reduced-carbohydrate diet (RCD) would improve insulin sensitivity and endothelial function compared with an isocaloric standard carbohydrate diet (SCD).
In this randomized, single-blinded, crossover trial, we studied 12 adults with type 1 diabetes. Participants completed both a one-week RCD and a one-week SCD, separated by a three-week washout. After each intervention, we measured insulin sensitivity using a hyperinsulinemic-euglycemic clamp and assessed endothelial function via brachial-artery flow-mediated vasodilation (FMD).
The RCD reduced total daily insulin doses by 16% compared with the SCD. Despite this reduction, insulin sensitivity did not improve (median glucose infusion rates: RCD 8.1 mg/kg FFM/min [IQR 6.7-10.1] vs. SCD 8.6 mg/kg FFM/min [7.0-11.0], p = 0.47). Similarly, endothelial function did not differ significantly (FMD after RCD 7.50% [3.25-15.5] vs. SCD 9.81% [4.96-14.3], p = 0.91). Although higher insulin doses correlated with lower insulin sensitivity under both conditions, lowering insulin dose through the RCD alone did not yield measurable improvements.
Although a one-week RCD significantly lowered insulin requirements, it failed to enhance insulin sensitivity or endothelial function in adults with type 1 diabetes. These findings underscore the complex and dynamic relationship between insulin exposure and cardiometabolic health. Similar basal overnight insulin delivery may have masked potential benefits by the time of testing, highlighting the need for further studies to refine strategies aimed at mitigating hyperinsulinemia's adverse effects.
ClinicalTrials.gov NCT04118374.
1型糖尿病患者外周注射胰岛素导致医源性外周高胰岛素血症，可能会增加胰岛素抵抗并损害内皮功能。我们推测，与等热量标准碳水化合物饮食（SCD）相比，通过为期一周的低碳水化合物饮食（RCD）降低医源性外周高胰岛素血症可改善胰岛素敏感性和内皮功能。
在这项随机、单盲、交叉试验中，我们研究了12名1型糖尿病成人患者。参与者完成了为期一周的RCD和为期一周的SCD，中间间隔三周的洗脱期。每次干预后，我们使用高胰岛素-正常血糖钳夹法测量胰岛素敏感性，并通过肱动脉血流介导的血管舒张（FMD）评估内皮功能。
与SCD相比，RCD使每日总胰岛素剂量降低了16%。尽管剂量降低，但胰岛素敏感性并未改善（中位葡萄糖输注速率：RCD为8.1mg/kg去脂体重/分钟[四分位间距6.7-10.1]，SCD为8.6mg/kg去脂体重/分钟[7.0-11.0]，p=0.47）。同样，内皮功能也没有显著差异（RCD后的FMD为7.50%[3.25-15.5]，SCD为9.81%[4.96-14.3]，p=0.91）。虽然在两种情况下较高的胰岛素剂量与较低的胰岛素敏感性相关，但仅通过RCD降低胰岛素剂量并未产生可测量的改善。
尽管为期一周的RCD显著降低了胰岛素需求，但它未能增强1型糖尿病成人患者的胰岛素敏感性或内皮功能。这些发现强调了胰岛素暴露与心脏代谢健康之间复杂而动态的关系。在测试时，相似的基础夜间胰岛素输注量可能掩盖了潜在益处，这突出了进一步研究以完善旨在减轻高胰岛素血症不良影响策略的必要性。
ClinicalTrials.gov NCT04118374。
