Positive association of the anti-aging protein α-Klotho with insulin resistance and its inverse L-shaped relationship with glycaemic control in the middle-aged and elderly population.

IF 3 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Endocrine Pub Date : 2024-10-01 Epub Date: 2024-05-18 DOI:10.1007/s12020-024-03874-5

Kai Wang, Jianing Liu

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引用次数: 0

Abstract

Purpose: α-Klotho has been linked to insulin resistance (IR) in basic research. However, experimental evidence is inconsistent, and there is a lack of data from human research. This study seeks to elucidate the association of α-Klotho with IR in a nationwide, multiracial population.

Methods: A total of 5289 participants aged 40-79 years were included in the National Health and Nutrition Examination Survey (NHANES) spanning 2007-2016. Serum α-Klotho was measured using enzyme-linked immunosorbent assays (ELISA), and IR was evaluated by the homeostatic model assessment of insulin resistance (HOMA-IR). Weighted multivariate logistic and linear regression analysis, subgroup analysis stratified by demographic characteristics, medical condition or obesity status, and sensitivity analysis using propensity score matching (PSM) were performed. Restricted cubic splines (RCS) were performed to explore the nonlinear relationship.

Results: In the fully adjusted logistic regression model, a significant positive association was observed between log-transformed α-Klotho and IR (OR = 3.63, 95% CI: 1.56, 8.45), particularly in males or nonobese individuals (P_interaction < 0.05). In the linear regression model, log₁₀(α-Klotho) was associated with fasting blood glucose (FBG, β = 1.25, 95% CI: 0.74, 1.76) and glycosylated hemoglobin (HbA1c, β = 0.49, 95% CI: 0.20, 0.77). RCS revealed an inverse L-shaped dose-response relationship of α-Klotho with FBG and HbA1c (P_nonlinear <0.05). Beyond the inflection point of log₁₀(α-Klotho) at 2.79, β coefficients sharply rose for these glycaemic control indicators.

Conclusion: The study provides clinical evidence supporting a positive association between α-Klotho and IR. Moreover, the inverse L-shaped relationship suggests that α-Klotho should reach a certain level to predict glycaemic changes effectively.

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中老年人群中抗衰老蛋白 α-Klotho 与胰岛素抵抗的正相关性及其与血糖控制的反 "L "型关系。

目的：在基础研究中，α-Klotho 与胰岛素抵抗（IR）有关。然而，实验证据并不一致，也缺乏人体研究数据。本研究试图在全国范围内的多种族人群中阐明α-Klotho与IR的关系：方法：在 2007-2016 年的美国国家健康与营养调查（NHANES）中，共纳入了 5289 名 40-79 岁的参与者。血清α-Klotho采用酶联免疫吸附测定法（ELISA）进行测定，IR采用胰岛素抵抗同态模型评估法（HOMA-IR）进行评估。研究人员进行了加权多变量逻辑和线性回归分析、按人口统计学特征、医疗状况或肥胖状况分层的亚组分析，以及使用倾向得分匹配法（PSM）进行的敏感性分析。为探讨非线性关系，还进行了限制性三次样条（RCS）分析：结果：在完全调整的逻辑回归模型中，观察到对数变换后的α-Klotho与IR之间存在显著的正相关（OR = 3.63，95% CI：1.56, 8.45），尤其是男性或女性。10（α-Klotho）与空腹血糖（FBG，β = 1.25，95% CI：0.74，1.76）和糖化血红蛋白（HbA1c，β = 0.49，95% CI：0.20，0.77）相关。RCS显示，α-Klotho与FBG和HbA1c呈反L型剂量反应关系（Pnonlinear 10(α-Klotho)为2.79，这些血糖控制指标的β系数急剧上升）：结论：本研究提供的临床证据支持α-Klotho 与 IR 之间存在正相关。此外，反 L 型关系表明，α-Klotho 应达到一定水平才能有效预测血糖变化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Endocrine ENDOCRINOLOGY & METABOLISM-

CiteScore

6.50

自引率

5.40%

发文量

295

审稿时长

1.5 months

期刊介绍： Well-established as a major journal in today’s rapidly advancing experimental and clinical research areas, Endocrine publishes original articles devoted to basic (including molecular, cellular and physiological studies), translational and clinical research in all the different fields of endocrinology and metabolism. Articles will be accepted based on peer-reviews, priority, and editorial decision. Invited reviews, mini-reviews and viewpoints on relevant pathophysiological and clinical topics, as well as Editorials on articles appearing in the Journal, are published. Unsolicited Editorials will be evaluated by the editorial team. Outcomes of scientific meetings, as well as guidelines and position statements, may be submitted. The Journal also considers special feature articles in the field of endocrine genetics and epigenetics, as well as articles devoted to novel methods and techniques in endocrinology. Endocrine covers controversial, clinical endocrine issues. Meta-analyses on endocrine and metabolic topics are also accepted. Descriptions of single clinical cases and/or small patients studies are not published unless of exceptional interest. However, reports of novel imaging studies and endocrine side effects in single patients may be considered. Research letters and letters to the editor related or unrelated to recently published articles can be submitted. Endocrine covers leading topics in endocrinology such as neuroendocrinology, pituitary and hypothalamic peptides, thyroid physiological and clinical aspects, bone and mineral metabolism and osteoporosis, obesity, lipid and energy metabolism and food intake control, insulin, Type 1 and Type 2 diabetes, hormones of male and female reproduction, adrenal diseases pediatric and geriatric endocrinology, endocrine hypertension and endocrine oncology.