文献：Melander O et al.Plasma Proneurotensin and Incidence of Diabetes, Cardiovascular Disease, Breast Cancer, and Mortality.JAMA. 2012;308(14):1469-1475.
Malmo Diet and Cancer Studyの参加者4632人を対象に、空腹時117-アミノ酸濃度の測定による血漿中プロニューロテンシンと糖尿病、心血管疾患、死亡率などとの関連を検討。空腹時のプロニューロテンシンと糖尿病、心血管疾患リスクが関連した。特に女性では乳癌、総死亡率、心血管疾患死亡率とも関連した。
Plasma Proneurotensin and Incidence of Diabetes, Cardiovascular Disease, Breast Cancer, and Mortality
Olle Melander, MD, PhD; Alan S. Maisel, MD; Peter Almgren, MSc; Jonas Manjer, MD, PhD; Mattias Belting, MD, PhD; Bo Hedblad, MD, PhD; Gunnar Engstrom, MD, PhD; Ute Kilger, PhD; Peter Nilsson, MD, PhD; Andreas Bergmann, PhD; Marju Orho-Melander, PhD
JAMA. 2012;308(14):1469-1475. doi:10.1001/jama.2012.12998.
ABSTRACT
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 Malmo 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.
