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白细胞端粒长度与负荷后血糖水平呈负相关,但与空腹血糖水平无关。

Leukocyte telomere length is inversely associated with post-load but not with fasting plasma glucose levels.

作者信息

Khalangot Mykola, Krasnienkov Dmytro, Vaiserman Alexander, Avilov Ivan, Kovtun Volodymir, Okhrimenko Nadia, Koliada Alexander, Kravchenko Victor

机构信息

1 Department of Endocrinology, Shupyk National Medical Academy of Postgraduate Education, Kyiv 04112, Ukraine.

2 Komisarenko Institute of Endocrinology and Metabolism, National Academy of Medical Sciences, Kyiv 04114, Ukraine.

出版信息

Exp Biol Med (Maywood). 2017 Apr;242(7):700-708. doi: 10.1177/1535370217694096. Epub 2017 Jan 1.

Abstract

Type 2 diabetes mellitus is characterized by shorter leukocyte telomere length, but the relationship between leukocyte telomere length and type 2 diabetes mellitus development is rather questioned. Fasting and post-load glycaemia associated with different types of insulin resistance and their relation with leukocyte telomere length remains unknown. We compared leukocyte telomere length and fasting or post-load glucose levels in persons who do not receive glucose lowering treatment. For 82 randomly selected rural residents of Ukraine, aged 45+, not previously diagnosed with type 2 diabetes mellitus, the WHO oral glucose tolerance test and anthropometric measurements were performed. Leukocyte telomere length was measured by standardized method of quantitative monochrome multiplex polymerase chain reaction in real time. Spearman's or Pearson's rank correlation was used for correlation analysis between fasting plasma glucose or 2-h post-load plasma glucose levels and leukocyte telomere length. Logistical regression models were used to evaluate risks of finding short or long telomeres associated with fasting plasma glucose or 2-h post-load plasma glucose levels. No association of fasting plasma glucose and leukocyte telomere length was revealed, whereas 2-h post-load plasma glucose levels demonstrated a negative correlation ( P < 0.01) with leukocyte telomere length. Waist circumference and systolic blood pressure were negatively related ( P = 0.03) with leukocyte telomere length in men. Oral glucose tolerance test result-based glycemic categories did not show differences between mean leukocyte telomere length in categories of normal fasting plasma glucose and 2-h post-load plasma glucose (NGT, n = 33); diabetes mellitus (DM), n = 18 and impaired fasting glucose/tolerance (IFG/IGT, n = 31) levels. A correlation relationship between leukocyte telomere length and 2-h post-load plasma glucose level in NGT; IFG/IGT and DM groups ( P = 0.027; 0.029 and 0.049, respectively) was revealed; the association between leukocyte telomere length and fasting plasma glucose was confirmed in DM group only ( P = 0.009). Increase of 2-h post-load plasma glucose (but not fasting plasma glucose) level improves the chances of revealing short telomeres: OR 1.52 (95% CI 1.04-2.22), P = 0.03. After the adjustment for age, gender, waist circumference, systolic blood pressure, and fasting plasma glucose, these phenomena remain significant. We conclude that 2-h post-load plasma glucose but not fasting plasma glucose is inversely associated with leukocyte telomere length. Impact statement • Contradictory epidemiologic data have been obtained about the link between the leucocyte telomere length (LTL) and diabetes. Type 2 diabetes (T2D) is likely to be pathophysiologically heterogeneous, but comparison of the association of LTL separately with fasting plasma glucose (FPG) and 2-h post-load plasma glucose (2hPG) levels has not been done before. Thus, the study of LTL changes associated with different types of hyperglycaemia, that largely determine the heterogenity of T2D is important. • In a population-based study of rural Ukrainians, we were the first to demonstrate that the increase of 2hPG (but not FPG) level increases the chances of revealing short telomeres. • The obtained data can help to clarify the relationship between the LTL shortening and different conditions of the insulin resistance (mainly liver resistance in high FPG and mostly muscle and adipose tissue resistance in high 2hPG).

摘要

2型糖尿病的特征是白细胞端粒长度较短,但白细胞端粒长度与2型糖尿病发生之间的关系备受质疑。与不同类型胰岛素抵抗相关的空腹及负荷后血糖及其与白细胞端粒长度的关系尚不清楚。我们比较了未接受降糖治疗者的白细胞端粒长度与空腹或负荷后血糖水平。对82名年龄在45岁及以上、此前未被诊断为2型糖尿病的乌克兰农村居民进行了随机抽样,进行了WHO口服葡萄糖耐量试验和人体测量。采用标准化的实时定量单色多重聚合酶链反应方法测量白细胞端粒长度。采用Spearman或Pearson等级相关分析空腹血糖或负荷后2小时血糖水平与白细胞端粒长度之间的相关性。采用逻辑回归模型评估与空腹血糖或负荷后2小时血糖水平相关的短端粒或长端粒的发现风险。未发现空腹血糖与白细胞端粒长度之间存在关联,而负荷后2小时血糖水平与白细胞端粒长度呈负相关(P < 0.01)。男性的腰围和收缩压与白细胞端粒长度呈负相关(P = 0.03)。基于口服葡萄糖耐量试验结果的血糖类别在空腹血糖正常和负荷后2小时血糖正常(NGT,n = 33);糖尿病(DM,n = 18)和空腹血糖受损/糖耐量受损(IFG/IGT,n = 31)水平的类别之间,平均白细胞端粒长度未显示出差异。在NGT;IFG/IGT和DM组中,白细胞端粒长度与负荷后2小时血糖水平之间存在相关性(分别为P = 0.027;0.029和0.049);仅在DM组中证实白细胞端粒长度与空腹血糖之间存在关联(P = 0.009)。负荷后2小时血糖(而非空腹血糖)水平升高会增加发现短端粒的几率:OR 1.52(95%CI 1.04 - 2.22),P = 0.03。在对年龄、性别、腰围、收缩压和空腹血糖进行校正后,这些现象仍然显著。我们得出结论,负荷后2小时血糖而非空腹血糖与白细胞端粒长度呈负相关。影响声明• 关于白细胞端粒长度(LTL)与糖尿病之间的联系,已获得相互矛盾的流行病学数据。2型糖尿病(T2D)在病理生理上可能具有异质性,但此前尚未分别比较LTL与空腹血糖(FPG)和负荷后2小时血糖(2hPG)水平之间的关联。因此,研究与不同类型高血糖相关的LTL变化很重要,因为高血糖在很大程度上决定了T2D的异质性。• 在一项基于乌克兰农村人群的研究中,我们首次证明2hPG(而非FPG)水平升高会增加发现短端粒的几率。• 所获得的数据有助于阐明LTL缩短与不同胰岛素抵抗状态(高FPG时主要为肝脏抵抗,高2hPG时主要为肌肉和脂肪组织抵抗)之间的关系。

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