Proneurotensin Linked to Diabetes, Cardiovascular Disease, Breast Cancer, and Death

Fasting proneurotensin is significantly associated with development of diabetes, cardiovascular disease (CVD), breast cancer, and total and cardiovascular mortality (JAMA 2012;308:1469–75). The findings, which showed proneurotensin to be elevated several years before disease onset, indicate that this analyte is a marker of underlying disease susceptibility rather than an expression of subclinical disease. The findings also warrant replication in other prospective studies and should encourage further research to test whether targeting the neurotensin system may in some way help prevent common diseases like diabetes and cardiovascular disease.

Neurotensin is a 13-amino acid peptide primarily expressed in the central nervous system and gastrointestinal tract. Food intake, especially fat, stimulates peripheral secretion of neurotensin, which in turn regulates gastrointestinal mobility and pancreatic and biliary secretion. Prior research has suggested that regulation of neurotensin secretion is disturbed in human obesity, but no other study has investigated whether neurotensin is related to obesity-associated diseases.

The authors evaluated 4,632 participants in a population-based study of the epidemiology of carotid artery disease. Median follow-up ranged from 13.2–15.7 years, depending on the disease in question. Because neurotensin is unstable both in vitro and in vivo, the authors measured proneurotensin, a stable 117-amino acid fragment from the N-terminal of the precursor neurotensin hormone. They used a chemiluminometric sandwich immunoassay to measure this analyte.

The investigators found each standard deviation increase of proneurotensin to be associated with increased disease, with hazard ratios of 1.17 for incident CVD, 1.28 for incident diabetes, and 1.29 for cardiovascular mortality. However, the relationship between proneurotensin and morbidity and mortality was significant only in women, and women had significantly higher levels of proneurotensin than men. Since estradiol has been shown to up-regulate expression of neurotensin, the authors speculate that higher proneurotensin levels in women and the negative outcomes in women may be due to their higher lifetime exposures to estrogen.

cTn I Strongest Mortality Predictor in Cardiac Amyloid Light-chain Amyloidosis

Increased cardiac troponin I (cTn I) is the strongest predictor of all-cause mortality in cardiac amyloid light-chain amyloidosis (CAL). Higher concentrations of cTn I also were associated with worse left ventricular and left atrial functions in CAL patients, making it a powerful tool in clinical and prognostic assessments of this patient population (Am J Cardiol 2012;110:1180–1184).

The findings come from a retrospective review of amyloid light-chain amyloidosis patients treated over a 7-year period at Memorial Sloan-Kettering Cancer Center in New York City. Of these 292 patients, 117 had CAL. The latter group was divided into two subgroups, those with normal cTn I, defined as <0.06 ng/mL, and those with increased cTn I, with levels ≥0.06 ng/mL. Patients with increased cTn I levels were older, had higher B-type natriuretic peptide (BNP) levels, and higher early/late mitral inflow velocity ratio and myocardial performance index. These patients also had a significantly shorter median survival in comparison to those with normal cTn I levels.

Initial univariate analysis identified many predictors of all-cause mortality, including increased cTn I, older age, male gender, New York Heart Association class III or IV, higher BNP, lower creatinine clearance, greater ventricular septal thickness, and higher myocardial performance index. However, in multivariate Cox survival analysis, only increased cTn I was a significant predictor of all-cause mortality.

As Renal Function Deteriorates, Levels of Progranulin Rise

Renal function is a strong independent predictor of serum levels of progranulin, a novel adipokine implicated in insulin resistance, which also is known as proepithelin, pc-cell-derived growth factor, acrogranin, and granulin-epithelin precursor (Diabetes Care 2012 DOI:10.2337/dc12–0220). The findings are consistent with the hypothesis that renal clearance is a major elimination route for circulating progranulin, and suggest that serum creatinine or estimated glomerular filtration rate always should be included in future studies examining progranulin physiology.

The authors measured progranulin via enzyme-linked immunosorbent assay and correlated levels of this analyte to anthropometric and biochemical parameters of renal function, inflammation, and glucose and lipid metabolism. The study involved 532 patients with stages 1–5 of chronic kidney disease (CKD).

The investigators found that median serum progranulin levels adjusted for age, sex, and body mass index were significantly different between CKD stages, ranging from 58.3 µg/L in stage 1 to 90.6 µg/L in stage 5. CKD stage was the strongest independent predictor of circulating progranulin, and high-sensitivity interleukin-6 and adiponectin also remained significantly and independently correlated with progranulin after multivariate regression analysis.

The authors called for further prospective studies to better elucidate progranulin's role in deteriorating kidney function and in metabolic and cardiovascular disease.

Blood-based POCT for HCV More Accurate than Rapid Tests, Oral-based POCT

A meta-analysis exploring the accuracy of rapid and point-of-care (POCT) screening tests for hepatitis C virus (HCV) found POCTs of serum, plasma, whole blood or oral fluid, and rapid diagnostic tests (RDTs) of serum and plasma all to be sufficiently accurate and suitable for screening initiatives (Ann Intern Med 2012;157:558–66). However, the researchers determined that POCTs of serum, plasma or whole blood have the highest accuracy, followed by RDTs of serum or plasma. POCTs of oral fluids were the least accurate.

Researchers from McGill University in Montreal and the London School of Hygiene and Tropical Medicine conducted the analysis with funding from the Canadian Institutes of Health Research. The authors reviewed 19 studies, of which 18 were meta-analyzed and stratified by specimen and test type. The studies examined 14 different tests by 13 different manufacturers.

The pooled sensitivity and specificity of serum and plasma POCTs was 98.9% and 99.7%, respectively, while whole blood and finger-stick POCTs had pooled sensitivity and specificity of 98.9% and 99.5%, respectively. Serum and plasma RDTs had pooled sensitivity and specificity of 98.4% and 98.6%, respectively. Oral fluid POCTs had the lowest pooled sensitivity and specificity, at 97.1% and 98.2%, respectively.

The authors suggested that the convenience and rapid turnaround times of POCTs, combined with the performance of these tests, show great potential for expanded first-line screening for HCV.