Abstract
Our aim was to identify serum microRNAs (miRNAs) in healthy humans which associate with future onset of both diabetes mellitus and cardiovascular disease. We performed global profiling of 753 mature human miRNAs in serum of 12 pilot subjects followed by measurement of 47 consistently expressed miRNAs in fasting serum of 553 healthy subjects from the baseline exam (1991-1994) of the population based Malmö Diet and Cancer Study Cardiovascular Cohort (MDC-CC), of whom 140 developed diabetes, and 169 cardiovascular diseases during follow-up. We used multivariate logistic regression to test individual miRNAs for association with incident diabetes and cardiovascular disease as compared to control subjects (n = 259). After Bonferroni correction and adjustment for age and sex, each SD increment of log-transformed miR-483-5p was significantly associated with both incident diabetes (OR = 1.48; 95% CI 1.18-1.84, P = 0.001) and cardiovascular disease (OR = 1.40; 95% CI 1.15, 1.72, P = 0.001). In cross sectional analysis, miR-483-5p was correlated with BMI (r = 0.162, P = 0.0001), fasting insulin (r = 0.156, P = 0.0002), HDL (r = -0.099, P = 0.02) and triglycerides (r = 0.11, P = 0.01). Adjustment for these metabolic risk factors, as well as traditional risk factors attenuated the miR-483-5p association with incident diabetes (OR = 1.28 95% CI 1.00-1.64, P = 0.049) whereas its association with incident cardiovascular disease remained virtually unchanged (OR = 1.46 95% CI, 1.18-1.81, P = 0.0005). In conclusion, miR-483-5p associates with both diabetes and cardiovascular disease. The association with diabetes seems partly mediated by obesity and insulin resistance, whereas the association with incident cardiovascular disease is independent of these metabolic factors and traditional cardiovascular disease risk factors.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Aged
-
Biomarkers / blood
-
Body Mass Index
-
Cardiovascular Diseases / diagnosis*
-
Cardiovascular Diseases / epidemiology
-
Cardiovascular Diseases / genetics
-
Cross-Sectional Studies
-
Diabetes Mellitus, Type 2 / diagnosis*
-
Diabetes Mellitus, Type 2 / epidemiology
-
Diabetes Mellitus, Type 2 / genetics
-
Female
-
Humans
-
Incidence
-
Insulin / blood
-
Insulin Resistance / genetics*
-
Lipoproteins, HDL / blood
-
Logistic Models
-
Male
-
MicroRNAs / blood*
-
Middle Aged
-
Obesity / genetics
-
Obesity / pathology*
-
Odds Ratio
-
Risk Factors
-
Triglycerides / blood
Substances
-
Biomarkers
-
Insulin
-
Lipoproteins, HDL
-
MIRN483 microRNA, human
-
MicroRNAs
-
Triglycerides
Grants and funding
This work was supported by the Swedish Foundation for Strategic Research (IRC-LUDC) and Swedish Research Council (SFO-EXODIAB). The project received grants from the Swedish Research Council (OM; LE [2016-0124]); Region Skåne-ALF/Skåne University Hospital (OM; LE), and Albert Påhlsson Foundation (LE; JLSE). OM also received support from the Knut and Alice Wallenberg Foundation; the Göran Gustafsson Foundation; the Swedish Heart- and Lung Foundation, and the Novo Nordisk Foundation. LE was also supported by The Swedish Diabetes Foundation (DIA2016-130). JLSE received funding from the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement No. 667191 (T2DSystems); Crafoord Foundation; Magnus Bergvalls Stiftelse and Syskonen Svenssons Foundation. LE also received support from Diabetes Research & Wellness Foundation. WG, OM, LE and JLSE contributed to study concept and design, statistical analyses, interpretation of data and drafted the manuscript. WG and JLSE performed the experiments. WG, OM, JLSE and LE made intellectual contributions to drafting and revising the manuscript and approved the final version.