Biomarker linked to risk of diabetes and cancer death
A cross-sectional association was found between plasma prostasin level and the risk of diabetes and cancer mortality in patients with high blood sugar.
Plasma prostasin levels had a cross-sectional association with cancer mortality risk and diabetes risk, which may help understand the link between diabetes and cancer.
Plasma prostasin levels act as a biomarker for tumors, primarily demonstrating an association with glucose metabolism and hyperglycemia-associated tumor pathology.
The study, published in Diabetology, used the Malmo Diet and Cancer study, which was conducted in Malmo, Sweden. The study sample includes participants from the Malmo Diet and Cancer Study Cardiovascular Cohort. Patients with prevalent diabetes were excluded from this study. Smoking habits, alcohol consumption, current medications, leisure-time physical activity, and level of education were obtained from participants as part of the demographic information.
There were 4658 participants, with a mean age (SD) of 57.5 (5.9) years; most were female (60.1%) and 361 (7.75%) had prevalent diabetes.
A cross-sectional analysis revealed an association between prostasin and diabetes, as the multivariate adjusted OR for the highest versus lowest quartile was 1.95 (95% CI, 1.39-2, 76). The OR for 1 SD of increased prostasin was 1.32 (95% CI, 1.16-1.50).
A longitudinal analysis that excluded participants with prevalent diabetes (4297 participants with a mean age of 57.3 [5.9] years) found a prostasin concentration of 8.44 (0.44) NPX for men and 8.18 (0.48) for women. This analysis also revealed that glomerular filtration rate (eGFR) values decreased as prostasin levels increased.
Other risk factors showed an upward trend from the first to the fourth quartile. Prostasin levels in non-diabetic patients correlated positively with fasting blood glucose levels, plasma insulin levels, and HOMA2-HR.
There were 702 patients who developed diabetes during a follow-up period of 21.9 (7.0) years. Participants with higher prostasin levels had a higher risk of diabetes, as the RR for diabetes in the highest and lowest prostasin quartile was 1.76 (95% CI, 1.41 -2.19) and one standard deviation increase in prostasin had an RR of 1.23 (95% CI, 1.13-1.34). The association was reduced after adjusting for fasting blood levels or HOMA2-IR, but was still significant.
Age, fasting glucose and eGFR were important factors in relation to diabetes risk, which was more evident in younger participants, those without impaired fasting glucose and in participants with impaired kidney function . The relationship between prostasin and diabetes was linear and not time-dependent.
651 participants died of cancer during an average follow-up period of 23.5 (6.1) years; prostasin was found to have a significant association with cancer mortality. Multivariate adjustment revealed that the HR was 1.43 (95% CI, 1.14-1.80) when comparing the highest quartile to the lowest quartile of prostasin and the increase of prostasin per standard deviation was 1.13 (95% CI, 1.04-1.23). These results remained the same after exclusion of cancer at baseline.
There was also an interaction between prostasin and fasting glucose for the risk of cancer mortality, where the RR for cancer mortality was 1.52 (95% CI, 1.07-2.16) and of 1.11 (95% CI, 1.01-1.21) per 1 SD increase in prostasin in participants with and without impaired fasting glucose at baseline.
The predictive ability of prostasin for cancer mortality and diabetes did not improve significantly.
There were some limitations to this study. Prostasin levels were measured in arbitrary units and could not be compared to absolute values. Bonferroni adjustments for biomarkers were not performed. Measurements of prostasin levels have been made with blood samples that have been frozen for over a decade, making storage stability uncertain. Serial measurements of prostasin and risk factors over time were not part of this study. The type of diabetes was also not determined.
The researchers concluded that plasma prostasin is a potential risk marker for the development of diabetes and risk of cancer mortality in people with high blood sugar.
Bao X, Xu B, Muhammad IF, Nilsson PM, Nilsson J, Engstrom G. Plasma prostasin: a new risk marker for diabetes incidence and cancer mortality. Diabetology. Published online August 4, 2022. doi:10.1007/s00125-022-05771-w