Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Texas Children's Hospital, Baylor College of Medicine, Houston, TX.
J Pediatr. 2018 May;196:208-216.e2. doi: 10.1016/j.jpeds.2017.12.052. Epub 2018 Feb 2.
Data regarding atherogenic dyslipidemia and the inflammation profile in youth with type 2 diabetes is limited and the effect of insulin therapy on these variables has not previously been studied in youth. We determined the impact of insulin therapy on lipid and inflammatory markers in youth with poorly controlled type 2 diabetes.
In the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) multicenter trial, 285 participants failed to sustain glycemic control on randomized treatment (primary outcome, glycated hemoglobin A1c [HbA1c] at ≥8% for 6 months); 363 maintained glycemic control (never reached primary outcome). Statins were used for a low-density lipoprotein cholesterol of ≥130 mg/dL. Upon reaching the primary outcome, insulin was started. Changes in lipids and inflammatory markers (slopes over time) were examined.
Progression of dyslipidemia was related to glycemic control. In those with the primary outcome, insulin therapy impacted HbA1c modestly, and dampened the increase in total cholesterol, low-density lipoprotein cholesterol, and total apolipoprotein B, although statin use increased from 8.6% to 22% year after the primary outcome. The increase in triglycerides and plasma nonesterified fatty acids stabilized after insulin was started, independent of HbA1c. There was an increase in high-sensitivity C-reactive protein that continued after insulin initiation, related to HbA1c and percent overweight.
Worsening dyslipidemia and inflammation over time raise concern regarding premature development of atherosclerosis in youth with type 2 diabetes. Insulin therapy has a limited benefit in the absence of glycemic control. Strategies to achieve better glycemic control are needed.
ClinicalTrials.gov: NCT00081328.
关于青少年 2 型糖尿病患者的动脉粥样硬化性血脂异常和炎症谱的数据有限，并且之前尚未研究过胰岛素治疗对这些变量的影响。我们旨在确定胰岛素治疗对控制不佳的青少年 2 型糖尿病患者的血脂和炎症标志物的影响。
在青少年和青年 2 型糖尿病治疗选择（TODAY）多中心试验中，285 名参与者在随机治疗时未能维持血糖控制（主要结局，糖化血红蛋白 A1c[HbA1c]≥8%持续 6 个月）；363 名参与者维持血糖控制（从未达到主要结局）。对于低密度脂蛋白胆固醇≥130mg/dL，使用他汀类药物。达到主要结局后，开始使用胰岛素。检查了血脂和炎症标志物的变化（随时间的斜率）。
血脂异常的进展与血糖控制有关。在达到主要结局的患者中，胰岛素治疗对 HbA1c 的影响适度，尽管他汀类药物的使用从主要结局后第一年的 8.6%增加到 22%，但抑制了总胆固醇、低密度脂蛋白胆固醇和总载脂蛋白 B 的增加。胰岛素开始后，甘油三酯和血浆非酯化脂肪酸的增加趋于稳定，与 HbA1c 无关。高敏 C 反应蛋白增加，在胰岛素开始后持续增加，与 HbA1c 和超重百分比有关。
随着时间的推移，血脂异常和炎症的恶化令人担忧，因为 2 型糖尿病青少年的动脉粥样硬化过早发展。在缺乏血糖控制的情况下，胰岛素治疗的益处有限。需要采取策略来实现更好的血糖控制。
ClinicalTrials.gov：NCT00081328。
