Diabetologia. 2016 Nov;59(11):2369-77. doi: 10.1007/s00125-016-4081-6. Epub 2016 Aug 26.
Genetic support for the causal role of insulin in coronary heart disease.
Tikkanen E1,2, Pirinen M3, Sarin AP3, Havulinna AS4, Männistö S4, Saltevo J5, Lokki ML6, Sinisalo J7, Lundqvist A4, Jula A4, Salomaa V4, Ripatti S8,9,10.
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Abstract
AIMS/HYPOTHESIS:
Epidemiological studies have identified several traits associated with CHD, but few of these have been shown to be causal risk factors and thus suitable targets for treatment. Our aim was to evaluate the causal role of a large set of known CHD risk factors using single-nucleotide polymorphisms (SNPs) as instrumental variables.
METHODS:
Based on published genome-wide association studies (GWASs), we estimated the associations between the established risk factors (blood lipids, obesity, glycaemic traits and BP) and CHD with two complementary approaches: (1) using summary statistics from GWASs to analyse the accordance of SNP effects on risk factors and on CHD; and (2) individual-level analysis where we constructed genetic risk scores (GRSs) in a large Finnish dataset (N = 26,554, CHD events n = 4016). We used a weighted regression-based method for summary-level data to evaluate the causality of risk factors. The associations between the GRSs and CHD in the Finnish dataset were evaluated with logistic and conditional logistic regression models.
RESULTS:
The summary-level data analysis revealed causal effects between glycaemic traits (insulin and glucose) and CHD. The individual-level data analysis supported the causal role of insulin, but not of glucose, on CHD. The GRS for insulin was associated with CHD in the Finnish cohort (OR 1.06 per SD in GRS, 95% CI 1.02, 1.10, p = 0.002).
CONCLUSIONS/INTERPRETATION:
These results support the causal role of insulin in the pathogenesis of CHD. Efficient treatment and prevention of insulin resistance is essential to prevent future CHD events.
KEYWORDS:
Epidemiology; Genetics; Insulin resistance; Insulin sensitivity
PMID: 27561896 DOI: 10.1007/s00125-016-4081-6
[PubMed - in process]

Conclusions
A short-term SFA-enriched diet induced whole body insulin resistance in both NGT and IGT subjects. Insulin resistance persisted overnight after the last SFA meal and was attenuated by one day of a healthy diet. This model offers opportunities for identifying early mechanisms and potential treatments of dietary saturated fat induced insulin resistance.

Ja SAFA aiheuttaa insuliiniresistenssiä. Laatikainen twiittailee tutkimuksen
A human model of dietary saturated fatty acid induced insulin resistance