Title: Somatostatin as a cardiometabolic risk marker

Main supervisor: Professor Olle Melander, Lund University

Reviewers: Professor Nils Wieurp, Lund University and Professor Bodil Ohlsson, Lund University

Abstract

Background

Sharper prediction of cardiovascular disease and diabetes is a prerequisite for better primary prevention, which could lead to reduced morbidity, mortality and societal cost. Somatostatin is a key regulator of metabolism, but its role in cardiometabolic disease is largely unstudied, partly because of its short half-life and low concentration in plasma.

Research questions

The goal of this thesis is to study whether somatostatin can be used to predict cardiometabolic disease and, because of its more stable nature in plasma, if it is possible to use the N-terminal cleavage product of prosomatostatin (NT-proSST) to do so. On an epidemiological level, we investigate the association between NT-proSST and cardiometabolic disease in a general population. We then study both somatostatin and NT-proSST in a fasting state and postprandially after meals of different fat content. This is done in an exploratory fashion to see what influences both these peptides, and how they relate to each other. We also look into genomic associations of elevated NT-proSST levels and common genetic variants.

Preliminary results

The epidemiological investigation is published and demonstrates that NT-proSST is significantly and independently associated with the development of cardiovascular disease, all-cause mortality and cardiovascular mortality in a general population. The dietary intervention is concluded. The preliminary results indicate that NT-proSST is significantly more elevated after a meal high in fat content, compared to a low-fat meal, and that secretion of somatostatin and NT-proSST are significantly associated after a high-fat meal, but not after a low-fat meal. We have found a significant association between elevated levels of NT-proSST and a single nucleotide polymorphism (rs8122936) that is previously known to be associated with cardiovascular disease.

Significance

Better prediction of cardiovascular disease is of great importance for the health care system. It would allow primary prevention both in the form of medication and lifestyle intervention to be given to the right individuals.

Published studies

Hedback T, Almgren P, Nilsson PM, Melander O. N-Terminal Prosomatostatin as a Risk Marker for Cardiovascular Disease and Diabetes in a General Population. J Clin Endocrinol Metab. Sep 2016;101(9):3437-44. doi:10.1210/jc.2016-1736