Plasma proneurotensin and incidence of diabetes, cardiovascular disease, breast cancer, and mortality.

CONTEXT

Neurotensin regulates both satiety and breast cancer growth in the experimental setting, but little is known about its role in the development of breast cancer or cardiometabolic disease in humans.

OBJECTIVE

To test if fasting plasma concentration of a stable 117-amino acid fragment from the neurotensin precursor hormone proneurotensin is associated with development of diabetes mellitus, cardiovascular disease, breast cancer, and mortality.

DESIGN, SETTING, AND PARTICIPANTS

Proneurotensin was measured in plasma from 4632 fasting participants of the population-based Malmö Diet and Cancer Study baseline examination 1991-1994. Multivariate Cox proportional hazards models were used to relate baseline proneurotensin to first events and death during long-term follow-up until January 2009, with median follow-up ranging from 13.2 to 15.7 years depending on the disease.

MAIN OUTCOME MEASURES

Incident diabetes mellitus, cardiovascular disease, breast cancer, and mortality.

RESULTS

Overall, proneurotensin (hazard ratio [HR] per SD increment of log-transformed proneurotensin) was related to risk of incident diabetes (142 events; HR, 1.28; 95% CI, 1.09-1.50; P = .003), cardiovascular disease (519 events; HR, 1.17; 95% CI, 1.07-1.27; P < .001), and cardiovascular mortality (174 events; HR, 1.29; 95% CI, 1.12-1.49; P = .001) with a significant interaction between proneurotensin and sex (P < .001) on risk of cardiovascular disease. Exclusively in women, proneurotensin was related to incident diabetes (74 events; HR, 1.41; 95% CI, 1.12-1.77; P = .003), cardiovascular disease (224 events; HR, 1.33; 95% CI, 1.17-1.51; P < .001), breast cancer (123 events; HR, 1.44; 95% CI, 1.21-1.71; P < .001), total mortality (285 events; HR, 1.13; 95% CI, 1.01-1.27; P = .03), and cardiovascular mortality (75 events; HR, 1.50; 95% CI, 1.20-1.87; P < .001).

CONCLUSION

Fasting proneurotensin was significantly associated with the development of diabetes, cardiovascular disease, breast cancer, and with total and cardiovascular mortality.