Role of Proneurotensin in Cardiometabolic Diseases

Description

The burden of cardiometabolic diseases is increasing worldwide. Early detection of high-risk individuals is essential for appropriate diagnosis, better treatment outcomes, quality of life and lower health related costs.

Aims
The overall aim of this thesis is to investigate the possible associations between plasma proneurotensin (Pro-NT) and risk of cardiovascular disease (CVD), type 2 diabetes (T2D), impaired glucose regulation, as well as diet-induced obesity in different study populations. As Pro-NT appears to be a novel risk marker for cardiometabolic morbidity and mortality, we also wanted to study the effects of dietary fat intake on circulating plasma Pro-NT and triglyceride levels. This thesis is based on epidemiological data from three population-based cohorts, The Malmö Preventive Project (MPP), The Malmö Diet and Cancer study- Cardiovascular Cohort (MDC-CC) and The MEDIM cohort (impact of Migration and Ethnicity on Diabetes in Malmö).

Paper I, in this cohort including an elderly population, we identified that Pro-NT predicts incident CVD in both genders, but incident T2D in women only, after 5.4 years of follow up.
Paper II, in a population-based cohort of Iraqi and Swedish born men and women, higher Pro-NT levels were observed both in the Iraqi- vs Swedish-born group. However, elevated plasma Pro-NT was associated with impaired glucose regulations assessed as insulin secretion and action and HbA1c in the Iraqi-population only.
Paper III, we found prompt increases in plasma Pro-NT every hour for four hours, after an oral lipid load in healthy individuals. Post-lipid rise of circulating plasma Pro-NT correlated with the changes in plasma triglyceride levels, irrespective of cream and olive oil.
Paper IV, in this longitudinal study, we identified that high Pro-NT levels predicted all-cause mortality (ACM) and cause- specific mortalities (CSM) due to CVD, gastrointestinaltract (GIT) diseases, mental and behavioral diseases, and diseases of unspecific causes, in both gender.

Conclusion
This thesis shows that circulating Pro-NT is a biomarker that in an elderly population predicts CVD in both gender, but T2D in women only Irrespective of gender, Pro-NT predicts ACM and CSM. Pro-NT is more strongly associated with impaired glucose regulation in a Middle Eastern immigrant population and may partly explain the increased T2D in this group. Furthermore, oral lipid intake increases Pro-NT levels, which facilitates triglyceride increase in blood in healthy individuals, supporting intestinal lipid absorption as being one key action of Pro-NT.

Period	2016 May 1 → 2022 May 12
Examinee/Supervised person	Ayesha Fawad
Examination/Supervision held at	Cardiovascular Research - Hypertension
Degree of Recognition	International