印度男性糖尿病前期和糖尿病患者中硬化蛋白与胰岛素敏感性及血糖参数关联的深入研究

An Insight Into the Association of Sclerostin With Insulin Sensitivity and Glycemic Parameters in Male Indian Prediabetic and Diabetic Population.

作者信息

Singh Praveen K, Naithani Manisha, Pathania Monika, Mirza Anissa A, Saha Sarama

机构信息

Biochemistry, All India Institute of Medical Sciences, Rishikesh, Rishikesh, IND.

Internal Medicine, All India Institute of Medical Sciences, Rishikesh, Rishikesh, IND.

出版信息

Cureus. 2022 Jul 21;14(7):e27123. doi: 10.7759/cureus.27123. eCollection 2022 Jul.

Abstract

Background Type 2 diabetes (T2D) is increasing day by day and creating a huge financial and social burden on the Indian population. Insulin resistance results in hyperglycemia, a condition that eventually causes prediabetes and Type 2 diabetes. The etiopathogenesis of T2D is still not clearly defined. Wnt signaling pathway is involved in pancreas development, islet function, insulin production, and secretion. Recent studies show that sclerostin, a Wnt signaling inhibitor, is associated with diabetes. The sclerostin level is altered as a function of race and ethnicity. However, no study has been conducted to observe the sclerostin level in prediabetic and diabetic individuals in the Indian population. Objectives The main objectives of the study are: to determine whether sclerostin is associated with glycemic parameters, serum insulin levels, insulin resistance/ sensitivity, beta-cell function, and adipose tissue insulin resistance (Adipo-IR). Methods This observational study was carried out at a tertiary care hospital, in Rishikesh, Uttarakhand, India. Individuals with T2D and prediabetes and healthy references were included in this study. Sclerostin and free fatty acids (FFA) were measured with the enzyme-linked immunosorbent assay (ELISA), and blood sugar, insulin, and glycated haemoglobin (HbA1c) were measured by the hexokinase, chemiluminescent, and chromatography methods, respectively. Messenger RNA (mRNA) was quantified by real-time polymerase chain reaction (PCR) using the SYBR Green protocol. Adipo-IR, homeostasis model assessment-estimated insulin resistance (HOMA-IR), homeostasis model assessment of β-cell function (HOMA-B), quantitative insulin sensitivity check index (QUICKI), and single point insulin sensitivity estimator (SPISE) indices were calculated. Results A total of 171 study participants were enrolled in type 2 diabetes, prediabetes, and controls groups, having 57 each in the group. There was a gradual increase in sclerostin levels from healthy [242.12(158.44)] to prediabetes [256.06(299.65)] and diabetes [465.76 (735.71)] with a significant (<0.001) difference from healthy reference. Sclerostin showed a significant positive correlation with fasting blood sugar (r=0.200; p=0.009), HbA1c (r=0.394; p<0.001) and free fatty acids (r=0.205; p=0.007) in total study participants. The SPISE index showed a significant positive correlation (r=0.269, p=0.043) in the prediabetic group. SOST, GLUT4, and insulin receptor (IR) mRNA expression all corroborate with the glycemic status. Conclusion Significantly higher expression of sclerostin (both protein and gene) in newly diagnosed T2D and prediabetes male patients, as well as significant association with SPISE index, suggest that sclerostin might be an indicator of pathophysiology related to insulin resistance, which is a characteristic feature of diabetes mellitus. However, the identification of causal relationships would warrant a large-scale prospective cohort study.

摘要

背景

2型糖尿病(T2D)日益增多,给印度人口带来了巨大的经济和社会负担。胰岛素抵抗会导致高血糖,这种情况最终会引发糖尿病前期和2型糖尿病。T2D的病因发病机制仍未明确界定。Wnt信号通路参与胰腺发育、胰岛功能、胰岛素产生及分泌。近期研究表明,Wnt信号抑制剂硬化蛋白与糖尿病有关。硬化蛋白水平因种族和民族而异。然而,尚未有研究观察印度人群中糖尿病前期和糖尿病个体的硬化蛋白水平。

目的

本研究的主要目的是:确定硬化蛋白是否与血糖参数、血清胰岛素水平、胰岛素抵抗/敏感性、β细胞功能及脂肪组织胰岛素抵抗(Adipo-IR)相关。

方法

本观察性研究在印度北阿坎德邦瑞诗凯诗的一家三级护理医院进行。本研究纳入了T2D和糖尿病前期个体以及健康对照。采用酶联免疫吸附测定(ELISA)法测定硬化蛋白和游离脂肪酸(FFA),分别采用己糖激酶法、化学发光法和色谱法测定血糖、胰岛素和糖化血红蛋白(HbA1c)。使用SYBR Green方案通过实时聚合酶链反应(PCR)对信使核糖核酸(mRNA)进行定量。计算Adipo-IR、稳态模型评估估计胰岛素抵抗(HOMA-IR)、β细胞功能稳态模型评估(HOMA-B)、定量胰岛素敏感性检查指数(QUICKI)和单点胰岛素敏感性估计器(SPISE)指数。

结果

2型糖尿病组、糖尿病前期组和对照组共纳入171名研究参与者,每组各57名。硬化蛋白水平从健康组[242.12(158.44)]到糖尿病前期组[256.06(299.65)]和糖尿病组[465.76(735.71)]逐渐升高,与健康对照相比差异有统计学意义(<0.001)。在所有研究参与者中,硬化蛋白与空腹血糖(r=0.200;p=0.009)、HbA1c(r=0.394;p<0.001)和游离脂肪酸(r=0.205;p=0.007)呈显著正相关。在糖尿病前期组中,SPISE指数呈显著正相关(r=0.269,p=0.043)。SOST mRNA、GLUT4 mRNA和胰岛素受体(IR)mRNA表达均与血糖状态相符。

结论

新诊断的T2D和糖尿病前期男性患者中硬化蛋白(蛋白质和基因)表达显著升高,以及与SPISE指数显著相关,表明硬化蛋白可能是与胰岛素抵抗相关的病理生理学指标,而胰岛素抵抗是糖尿病的一个特征。然而,确定因果关系需要进行大规模前瞻性队列研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/766d/9392653/36e44c48b028/cureus-0014-00000027123-i01.jpg

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