Retnakaran Ravi, Pu Jiajie, Hanley Anthony J, Connelly Philip W, Sermer Mathew, Zinman Bernard
Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Canada.
Division of Endocrinology, University of Toronto, Toronto, Canada.
EClinicalMedicine. 2023 Dec 13;67:102363. doi: 10.1016/j.eclinm.2023.102363. eCollection 2024 Jan.
The cardiometabolic implications of postprandial hyperinsulinemia are unclear with recent studies suggesting both adverse and beneficial associations. We aimed to evaluate the longitudinal cardiometabolic implications of the post-challenge insulin secretory response over 4-years follow-up.
In this prospective cohort study, conducted in Toronto (Ontario, Canada), women comprising the full range of antepartum glucose tolerance were recruited in pregnancy (at the time of glucose tolerance screening, late in the second trimester) to undergo cardiometabolic testing in the years thereafter. Participants underwent oral glucose tolerance tests (OGTT) at 1-year, 3-years, and 5-years postpartum, enabling serial assessment of cardiovascular risk factors, glucose tolerance, insulin sensitivity or resistance (Matsuda index, HOMA-IR), and beta-cell function-via Insulin Secretion-Sensitivity Index-2 (ISSI-2) and insulinogenic index/HOMA-IR (IGI/HOMA-IR). Baseline post-challenge insulinemia was assessed with the corrected insulin response (CIR) at 1-year. Cardiometabolic factors were compared between baseline CIR tertiles.
Between Oct 23, 2003 and March 31, 2014, 306 women were enrolled. In this study population, there was progressive worsening of waist circumference (p = 0.016), HDL (p = 0.018), CRP (p = 0.006), and insulin sensitivity (p < 0.001) from the lowest to middle to highest tertile of CIR at 1-year. However, these adverse features were accompanied by progressively better beta-cell function (both p < 0.001), coupled with lower fasting and 2-h glucose on the OGTT (both p < 0.001). On adjusted longitudinal analyses, higher CIR tertile at 1-year was independently associated with (i) higher ISSI-2 and IGI/HOMA-IR and (ii) lower fasting and 2-h glucose at both 3-years and 5-years (all p < 0.001), but was not associated with BMI, waist, lipids, CRP or insulin sensitivity/resistance. The highest CIR tertile at 1-year predicted lower risk of pre-diabetes or diabetes at both 3-years (adjusted OR = 0.19; 95% CI 0.08-0.45) and 5-years (aOR = 0.18; 0.08-0.39), relative to the lowest tertile.
A robust post-challenge insulin secretory response does not indicate adverse cardiometabolic health but, rather, portends favourable metabolic function in the years to come. Future long-term study of the implications of the post-challenge insulinemic response is warranted.
Canadian Institutes of Health Research.
餐后高胰岛素血症对心脏代谢的影响尚不清楚，近期研究表明其既存在不良关联也有有益关联。我们旨在评估4年随访期间挑战后胰岛素分泌反应对心脏代谢的纵向影响。
在加拿大多伦多进行的这项前瞻性队列研究中，招募了孕期（孕中期晚期进行糖耐量筛查时）具有各种产前糖耐量情况的女性，以便在之后几年进行心脏代谢测试。参与者在产后1年、3年和5年接受口服葡萄糖耐量试验（OGTT），从而能够对心血管危险因素、糖耐量、胰岛素敏感性或抵抗（松田指数、HOMA-IR）以及β细胞功能进行系列评估，评估指标包括胰岛素分泌敏感性指数-2（ISSI-2）和胰岛素生成指数/HOMA-IR（IGI/HOMA-IR）。1年时通过校正胰岛素反应（CIR）评估基线挑战后胰岛素血症。比较基线CIR三分位数之间的心脏代谢因素。
在2003年10月23日至2014年3月31日期间，共纳入306名女性。在该研究人群中，从1年时CIR的最低三分位数到中间三分位数再到最高三分位数，腰围（p = 0.016）、高密度脂蛋白（HDL，p = 0.018）、C反应蛋白（CRP，p = 0.006）和胰岛素敏感性（p < 0.001）呈逐渐恶化趋势。然而，这些不良特征伴随着逐渐改善的β细胞功能（p均< 0.001），同时OGTT上的空腹血糖和2小时血糖较低（p均< 0.001）。在调整后的纵向分析中，1年时较高的CIR三分位数与以下因素独立相关：（i）较高的ISSI-2和IGI/HOMA-IR；（ii）3年和5年时较低的空腹血糖和2小时血糖（p均< 0.001），但与体重指数（BMI）、腰围、血脂、CRP或胰岛素敏感性/抵抗无关。相对于最低三分位数，1年时CIR最高三分位数预测3年（调整后OR = 0.19；95%CI 0.08 - 0.45）和5年（调整后OR = 0.18；0.08 - 0.39）时患糖尿病前期或糖尿病的风险较低。
强烈的挑战后胰岛素分泌反应并不表明心脏代谢健康不良，相反，预示着未来几年良好的代谢功能。未来有必要对挑战后胰岛素血症反应的影响进行长期研究。
加拿大卫生研究院。
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