Plasma prostasin: a novel risk marker for incidence of diabetes and cancer mortality,Diabetologia

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Plasma prostasin: a novel risk marker for incidence of diabetes and cancer mortality
Diabetologia ( IF 8.4 ) Pub Date : 2022-08-04 , DOI: 10.1007/s00125-022-05771-w
Xue Bao _{1,

2} , Biao Xu ₁ , Iram Faqir Muhammad ₂ , Peter M Nilsson ₂ , Jan Nilsson ₂ , Gunnar Engström ₂

Affiliation

Aims/hypothesis

Diabetes is associated with an increased risk of cancer. Prostasin is an epithelial sodium channel stimulator that has been associated with suppression of tumours, glucose metabolism and hyperglycaemia-associated tumour pathology. However, the association between prostasin, diabetes and cancer mortality has not been well investigated in humans. We aim to investigate the associations between plasma prostasin and diabetes, and to explore whether prostasin has an effect on cancer mortality risk in individuals with hyperglycaemia.

Methods

Plasma prostasin was measured using samples from the Malmö Diet and Cancer Study Cardiovascular Cohort, and statistical analysis was performed from both sex-specific quartiles and per 1 SD. The cross-sectional association between plasma prostasin and diabetes was first studied in 4658 participants (age 57.5 ± 5.9 years, 39.9% men). After excluding 361 with prevalent diabetes, the associations of prostasin with incident diabetes and cancer mortality risk were assessed using Cox regression analysis. The interactions between prostasin and blood glucose levels as well as other covariates were tested.

Results

The adjusted OR for prevalent diabetes in the 4th vs 1st quartile of prostasin concentrations was 1.95 (95% CI 1.39, 2.76) (p for trend <0.0001). During mean follow-up periods of 21.9 ± 7.0 and 23.5 ± 6.1 years, respectively, 702 participants developed diabetes and 651 died from cancer. Prostasin was significantly associated with the incidence of diabetes. The adjusted HR for diabetes in the 4th vs 1st quartile of prostasin concentrations was 1.76 (95% CI 1.41, 2.19) (p for trend <0.0001). Prostasin was also associated with cancer mortality There was a significant interaction between prostasin and fasting blood glucose for cancer mortality risk (p for interaction =0.022), with a stronger association observed in individuals with impaired fasting blood glucose levels at baseline (HR per 1 SD change 1.52; 95% CI 1.07, 2.16; p=0.019).

Conclusions/interpretation

Plasma prostasin levels are positively associated with diabetes risk and with cancer mortality risk, especially in individuals with high blood glucose levels, which may shed new light on the relationship between diabetes and cancer.

Graphical abstract

中文翻译：

血浆前列腺素：糖尿病发病率和癌症死亡率的新风险标志物

目标/假设

糖尿病与癌症风险增加有关。前列腺素是一种上皮钠通道刺激剂，与抑制肿瘤、葡萄糖代谢和高血糖相关的肿瘤病理学有关。然而，前列腺素、糖尿病和癌症死亡率之间的关系尚未在人类中得到很好的研究。我们旨在研究血浆前列腺素与糖尿病之间的关联，并探讨前列腺素是否对高血糖患者的癌症死亡风险有影响。

方法

使用来自马尔默饮食和癌症研究心血管队列的样本测量血浆前列腺素，并从性别特异性四分位数和每 1 SD 进行统计分析。血浆前列腺素与糖尿病之间的横断面关联首先在 4658 名参与者（年龄 57.5 ± 5.9 岁，39.9% 男性）中进行了研究。在排除 361 名糖尿病患者后，使用 Cox 回归分析评估前列腺素与糖尿病和癌症死亡风险之间的关联。测试了前列腺素和血糖水平以及其他协变量之间的相互作用。

结果

前列腺素浓度第 4 和第 1 四分位数中流行糖尿病的校正 OR 为 1.95（95% CI 1.39, 2.76）（趋势p <0.0001）。在分别为 21.9 ± 7.0 和 23.5 ± 6.1 年的平均随访期间，702 名参与者患上了糖尿病，651 人死于癌症。前列腺素与糖尿病的发病率显着相关。在前列腺素浓度的第 4 和第 1 个四分位数中，糖尿病的调整后 HR 为 1.76（95% CI 1.41, 2.19）（趋势p <0.0001）。前列腺素也与癌症死亡率相关前列腺素与空腹血糖之间存在显着的相互作用，从而降低癌症死亡率（p交互作用 = 0.022），在基线空腹血糖水平受损的个体中观察到更强的相关性（HR 每 1 SD 变化 1.52；95% CI 1.07, 2.16；p = 0.019）。