瘦素和脂联素与非裔美国人 2 型糖尿病发病的相关性：杰克逊心脏研究。
Associations of leptin and adiponectin with incident type 2 diabetes and interactions among African Americans: the Jackson heart study.
机构信息
Department of Epidemiology and Biostatistics, Indiana University School of Public Health, 1025 E. 7th Street, Bloomington, IN, 47405, USA.
Henry M Jackson Foundation for the advancement of Military Medicine, Bethesda, MD, USA.
出版信息
BMC Endocr Disord. 2020 Mar 4;20(1):31. doi: 10.1186/s12902-020-0511-z.
BACKGROUND
Growing evidence suggests that leptin is critical for glycemic control. Impaired leptin signaling may also contribute to low adiponectin expression in obese individuals. We assessed the association of leptin and adiponectin with incident type 2 diabetes (T2D), their interactions with sex and obesity status, and mediation by insulin resistance.
METHODS
We included study participants from the Jackson Heart Study, a prospective cohort of adult African Americans in Jackson, Mississippi, that were free of T2D at the baseline Exam 1. Incident T2D was defined as new cases at Exam 2 or Exam 3. We created separate Cox regression models (hazard ratios per log-transformed ng/mL of leptin and adiponectin) with and without insulin resistance, HOMA-IR. Mediation by insulin resistance was analyzed. Several interactions were assessed, including by sex, HbA1c, and obesity.
RESULTS
Among our 3363 participants (mean age 53 years, 63% women), 584 developed incident T2D. Leptin was directly associated with incident T2D when modeled without HOMA-IR (HR = 1.29, 95% CI = 1.05-1.58). This direct association between leptin and T2D was significant among men (HR = 1.33, 95% CI = 1.05-1.69), but nonsignificant among women (HR = 1.24, 95% CI = 0.94-1.64); statistical interaction with sex was nonsignificant (p = 0.65). The associations in all participants and in men were nullified by HOMA-IR (HR = 0.99, 95% CI = 0.80-1.22; HR = 1.00, 95% CI = 0.78-1.28, respectively), indicating mediation through insulin resistance (proportion mediated: 1.04), and were not observed in abdominally obese participants. Adiponectin was inversely associated with T2D even after adjustment for HOMA-IR in women (HR = 0.68, 95% CI = 0.55-0.84), but not in men (HR = 0.80, 95% CI = 0.62-1.04). The inverse association was present only among abdominally obese participants, and persisted after adjustment for HOMA-IR.
CONCLUSIONS
Among African Americans in the Jackson Heart Study the association of leptin with incident type 2 diabetes was mediated by insulin resistance. This association was present only among abdominally non-obese participants. Differences by sex appeared: men showed a significant association mediated by insulin resistance. Among abdominally obese participants, adiponectin was inversely associated with incident T2D even after adjustment for HOMA-IR. Our results should inform future clinical trials that aim to reduce the burden of type 2 diabetes through the modification of serum levels of leptin and adiponectin.
背景
越来越多的证据表明，瘦素对于血糖控制至关重要。瘦素信号受损也可能导致肥胖个体中脂联素表达降低。我们评估了瘦素和脂联素与 2 型糖尿病（T2D）发病的相关性，以及它们与性别和肥胖状态的相互作用，以及胰岛素抵抗的中介作用。
方法
我们纳入了来自杰克逊心脏研究（Jackson Heart Study）的研究参与者，这是密西西比州杰克逊市的一项成年非裔美国人前瞻性队列研究，基线检查 1 时无 T2D。新诊断的 T2D 定义为在检查 2 或检查 3 时出现新病例。我们分别创建了 Cox 回归模型（每 ng/mL 瘦素和脂联素的对数转换的风险比），包括和不包括胰岛素抵抗（HOMA-IR）。分析了胰岛素抵抗的中介作用。评估了几种相互作用，包括性别、HbA1c 和肥胖。
结果
在我们的 3363 名参与者中（平均年龄 53 岁，63%为女性），有 584 人发生了新诊断的 T2D。在不考虑 HOMA-IR 的情况下，瘦素与 T2D 的发病直接相关（HR=1.29，95%CI=1.05-1.58）。这种瘦素与 T2D 之间的直接关联在男性中具有统计学意义（HR=1.33，95%CI=1.05-1.69），但在女性中无统计学意义（HR=1.24，95%CI=0.94-1.64）；性别间的统计学交互作用无统计学意义（p=0.65）。在所有参与者和男性中的关联在考虑 HOMA-IR 后均被消除（HR=0.99，95%CI=0.80-1.22；HR=1.00，95%CI=0.78-1.28，分别），表明通过胰岛素抵抗进行了中介（中介比例：1.04），并且在腹部肥胖的参与者中没有观察到这种关联。脂联素与 T2D 呈负相关，即使在女性中考虑了 HOMA-IR 后也是如此（HR=0.68，95%CI=0.55-0.84），但在男性中并非如此（HR=0.80，95%CI=0.62-1.04）。这种负相关仅存在于腹部肥胖的参与者中，并且在调整 HOMA-IR 后仍然存在。
结论
在杰克逊心脏研究中的非裔美国人中，瘦素与 2 型糖尿病发病的相关性通过胰岛素抵抗进行了中介。这种关联仅存在于非腹部肥胖的参与者中。性别差异似乎存在：男性表现出通过胰岛素抵抗介导的显著关联。在腹部肥胖的参与者中，脂联素与 T2D 的发病呈负相关，即使在调整 HOMA-IR 后也是如此。我们的研究结果应该为未来旨在通过改变瘦素和脂联素血清水平来降低 2 型糖尿病负担的临床试验提供信息。
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