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生长分化因子 15 作为印度人群肥胖前期和 2 型糖尿病的生物标志物:一项病例对照研究。

Growth Differentiation Factor-15 as a Biomarker of Obese Pre-diabetes and Type 2 Diabetes Mellitus in Indian Subjects: A Case-control Study.

机构信息

Department of Biochemistry, AIIMS, Jodhpur, Rajasthan,India.

Department of Biochemistry, AIIMS, Jodhpur, Rajasthan, India.

出版信息

Curr Diabetes Rev. 2022;18(1):e010321189862. doi: 10.2174/1573399817666210104101739.

DOI:10.2174/1573399817666210104101739
PMID:33397240
Abstract

BACKGROUND

Type 2 diabetes mellitus (T2DM) is an ever-growing epidemic in India and poses significant morbidity, mortality, and socioeconomic burden.

INTRODUCTION

Growth differentiation factor-15 (GDF15) is a stress-responsive cytokine, increased in T2DM patients compared to control subjects without the disease. We aimed to assess whether serum GDF15 and adipose tissue GDF15 expression can differentiate between obese pre-diabetes and T2DM and control populations.

METHODOLOGY

We recruited 156 individuals including 73 type 2 diabetes, 30 pre-diabetes, and 53 healthy controls. Clinical history, anthropometric measurements and biochemical profiling were taken. Insulin resistance indices were calculated following HOMA models. Serum GDF15 was measured by sandwich ELISA. Visceral adipose tissue (VAT) expression of GDF15 was observed in 17 T2DM patients and 29 controls using SYBR Green chemistry in RT-PCR using GAPDH as the housekeeping gene. The data were analyzed on R programming platform using RStudio.

RESULTS

Serum GDF15 was significantly higher (p<0.001) in T2DM subjects (median 1445.47 pg/mL) compared to pre-diabetes (627.85 pg/mL) and healthy controls (609.01 pg/mL). Using the ΔΔCt method, the VAT GDF15 expression was 1.54 fold and 1.57 fold upregulated in T2DM (n=17) compared to control subjects (n=29), and obese (n=12) compared to non-obese (n=34)subjects, respectively. The optimal cut-off point following Youden's index method was found to be 868.09 pg/mL. ROC curve analysis revealed that serum GDF15 had a sensitivity, specificity, and area under the curve (AUC) of 90.41%, 79.52%, and 0.892 respectively. GDF15 levels were significantly associated with age, BMI, HbA1c, fasting blood sugar, and insulin resistance indices.

CONCLUSION

Hence, serum GDF15 is a biomarker for T2DM patients in our study population from Western India. However, larger prospective cohorts are necessary to validate this claim.

摘要

背景

2 型糖尿病(T2DM)在印度是一种日益严重的流行疾病,给患者带来了严重的发病率、死亡率和社会经济负担。

介绍

生长分化因子 15(GDF15)是一种应激反应性细胞因子,在 T2DM 患者中比没有该疾病的对照组升高。我们旨在评估血清 GDF15 和脂肪组织 GDF15 表达是否能区分肥胖前期糖尿病和 T2DM 患者与对照组人群。

方法

我们招募了 156 名个体,包括 73 名 2 型糖尿病患者、30 名前期糖尿病患者和 53 名健康对照组。记录了临床病史、人体测量学测量和生化特征。使用 HOMA 模型计算胰岛素抵抗指数。采用夹心 ELISA 法测定血清 GDF15。使用 SYBR Green 化学法,在 RT-PCR 中以 GAPDH 为管家基因,观察了 17 名 T2DM 患者和 29 名对照组的内脏脂肪组织(VAT)GDF15 的表达。数据在 R 编程平台上使用 RStudio 进行分析。

结果

T2DM 患者的血清 GDF15 显著升高(p<0.001)(中位数 1445.47 pg/mL),与前期糖尿病(627.85 pg/mL)和健康对照组(609.01 pg/mL)相比。使用ΔΔCt 法,与对照组(n=29)相比,T2DM(n=17)和肥胖组(n=12)中 VAT GDF15 的表达分别上调了 1.54 倍和 1.57 倍。根据 Youden 指数法确定的最佳截断点为 868.09 pg/mL。ROC 曲线分析显示,血清 GDF15 的敏感性、特异性和曲线下面积(AUC)分别为 90.41%、79.52%和 0.892。GDF15 水平与年龄、BMI、HbA1c、空腹血糖和胰岛素抵抗指数显著相关。

结论

因此,血清 GDF15 是我们来自印度西部研究人群中 T2DM 患者的生物标志物。然而,需要更大的前瞻性队列来验证这一说法。

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