美国印第安 2 型糖尿病患者并发症轨迹的决定因素。
The determinants of complication trajectories in American Indians with type 2 diabetes.
机构信息
Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.
Division of Pediatric Neurology, Dr. Behcet Uz Children's Hospital, Izmir, Turkey.
出版信息
JCI Insight. 2021 May 24;6(10):146849. doi: 10.1172/jci.insight.146849.
BACKGROUNDWe aimed to determine whether metabolic syndrome (MetS) affects longitudinal trajectories of diabetic complications, including neuropathy, cardiovascular autonomic neuropathy (CAN), and kidney disease in American Indians with type 2 diabetes.METHODSWe performed a prospective study where participants underwent annual metabolic phenotyping and outcome measurements. The updated National Cholesterol Education Program criteria were used to define MetS and its individual components, using BMI instead of waist circumference. Neuropathy was defined using the Michigan Neuropathy Screening Instrument index, CAN with the expiration/inspiration ratio, and kidney disease with glomerular filtration rate. Mixed-effects models were used to evaluate associations between MetS and these outcomes.RESULTSWe enrolled 141 participants: 73.1% female, a mean (±SD) age of 49.8 (12.3), and a diabetes duration of 19.6 years (9.7 years) who were followed for a mean of 3.1 years (1.7 years). MetS components were stable during follow-up except for declining obesity and cholesterol. Neuropathy (point estimate [PE]: 0.30, 95% CI: 0.24, 0.35) and kidney disease (PE: -14.2, 95% CI: -16.8, -11.4) worsened over time, but CAN did not (PE: -0.002, 95% CI: -0.006, 0.002). We found a significant interaction between the number of MetS components and time for neuropathy (PE: 0.05, 95% CI: 0.01-0.10) but not CAN (PE: -0.003, 95% CI: -0.007, 0.001) or kidney disease (PE: -0.69, 95% CI: -3.16, 1.76). Systolic blood pressure (SBP, unit = 10 mmHg) was associated with each complication: neuropathy (PE: 0.23, 95% CI: 0.07, 0.39), CAN (PE: -0.02, 95% CI: -0.03, -0.02), and kidney disease (PE: -10.2, 95% CI: -15.4, -5.1).CONCLUSIONIn participants with longstanding diabetes, neuropathy and kidney disease worsened during follow-up, despite stable to improving MetS components, suggesting that early metabolic intervention is necessary to prevent complications in such patients. Additionally, the number of MetS components was associated with an increased rate of neuropathy progression, and SBP was associated with each complication.FUNDINGThe following are funding sources: NIH T32NS0007222, NIH R24DK082841, NIH R21NS102924, NIH R01DK115687, the Intramural Program of the NIDDK, the NeuroNetwork for Emerging Therapies, the Robert and Katherine Jacobs Environmental Health Initiative, the Robert E. Nederlander Sr. Program for Alzheimer's Research, and the Sinai Medical Staff Foundation.TRIAL REGISTRATIONClinicalTrials.gov, NCT00340678.
背景
我们旨在确定代谢综合征（MetS）是否会影响美国印第安人 2 型糖尿病患者的糖尿病并发症的纵向轨迹，包括神经病变、心血管自主神经病变（CAN）和肾脏疾病。
方法
我们进行了一项前瞻性研究，参与者每年进行代谢表型分析和结果测量。采用更新的国家胆固醇教育计划标准，使用 BMI 代替腰围来定义 MetS 及其个体成分。使用密歇根神经病变筛查工具指数定义神经病变，使用呼气/吸气比定义 CAN，使用肾小球滤过率定义肾脏疾病。采用混合效应模型评估 MetS 与这些结局之间的关系。
结果
我们共纳入 141 名参与者：73.1%为女性，平均（±SD）年龄为 49.8（12.3）岁，糖尿病病程为 19.6 年（9.7 年），平均随访时间为 3.1 年（1.7 年）。在随访期间，MetS 成分除肥胖和胆固醇下降外保持稳定。神经病变（点估计[PE]：0.30，95%CI：0.24，0.35）和肾脏疾病（PE：-14.2，95%CI：-16.8，-11.4）随时间恶化，但 CAN 没有（PE：-0.002，95%CI：-0.006，0.002）。我们发现 MetS 成分数量与神经病变时间之间存在显著的交互作用（PE：0.05，95%CI：0.01-0.10），但与 CAN（PE：-0.003，95%CI：-0.007，0.001）或肾脏疾病（PE：-0.69，95%CI：-3.16，1.76）无关。收缩压（SBP，单位为 10mmHg）与每种并发症均相关：神经病变（PE：0.23，95%CI：0.07，0.39）、CAN（PE：-0.02，95%CI：-0.03，-0.02）和肾脏疾病（PE：-10.2，95%CI：-15.4，-5.1）。
结论
在长期患有糖尿病的参与者中，尽管 MetS 成分稳定或改善，但神经病变和肾脏疾病在随访期间仍恶化，这表明需要早期进行代谢干预以预防此类患者的并发症。此外，MetS 成分的数量与神经病变进展的速度增加有关，SBP 与每种并发症均相关。
资助
美国国立卫生研究院 T32NS0007222、美国国立卫生研究院 R24DK082841、美国国立卫生研究院 R21NS102924、美国国立卫生研究院 R01DK115687、国家糖尿病、消化和肾脏疾病研究所内部计划、新兴治疗神经网络、罗伯特和凯瑟琳·雅各布斯环境健康倡议、罗伯特·E·内德兰德高级阿尔茨海默病研究计划和西奈山医务人员基金会。
临床试验注册
ClinicalTrials.gov，NCT00340678。
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