Plasma Proneurotensin and Incidence of Diabetes, Cardiovascular Disease, Breast Cancer, and Mortality

Study Questions:

What is the relationship between plasma levels of proneurotensin and diabetes mellitus (DM), cardiovascular disease (CVD), breast cancer (CA), and mortality?

Methods:

Proneurotensin plasma levels were measured from 4,632 fasting population-based participants. Multivariate Cox proportional hazards models were used to relate baseline proneurotensin to first events and death during a median follow-up ranging from 13.2 to 15.7 years, depending on the disease. Outcome measures were incident DM, CVD, breast CA, and mortality.

Results:

Proneurotensin was related to risk of incident DM (142 events; hazard ratio [HR], 1.28; p = 0.003), CVD (519 events; HR, 1.17; p < 0.001), and CV mortality (174 events; HR, 1.29; p = 0.001) with a significant interaction between proneurotensin and sex (p < 0.001) on risk of CVD. In women specifically, proneurotensin was related to incident DM (74 events; HR, 1.41; p = 0.003), CVD (224 events; HR, 1.33; p < 0.001), breast CA (123 events; HR, 1.44; p < 0.001), total mortality (285 events; HR, 1.13; p = 0.03), and CV mortality (75 events; HR, 1.50; p < 0.001).

Conclusions:

The authors concluded that fasting proneurotensin was significantly associated with the development of DM, CVD, breast CA, and with total and CV mortality.

Perspective:

Neurotensin is produced by cells from the central nervous system and gastrointestinal (GI) tract. It is secreted in response to food/fat intake and acts to suppress appetite and regulate GI motility, although regulation of neurotension may be altered in obesity. Preclinical studies have demonstrated that neurotensin may also promote neoplastic tissue growth and possibly atherosclerosis via stimulation of various receptors. By measuring the stable, N-terminal fragment of neurotensin, these authors demonstrated an association with multiple morbidities, suggesting that this hormone could be one of the links between obesity and adverse outcomes. The causal nature of these relationships, as well as the specificity of some of these endpoints for women, will require further study.

Keywords: Biological Markers, Cardiovascular Diseases, Breast Neoplasms, Neurotensin


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