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A genetic risk score for fasting plasma glucose is independently associated with arterial stiffness: a Mendelian randomization study.

ABSTRACT: BACKGROUND:Arterial stiffness is known to be associated with a number of clinical conditions including hypertension, diabetes and dyslipidemia, and may predict cardiovascular events and mortality. However, causal links are hard to establish. Results from genome-wide association studies have identified only a few single nucleotide polymorphisms associated with arterial stiffness, the results have been inconsistent between studies and overlap with other clinical conditions is lacking. Our aim was to investigate a potential shared set of risk single nucleotide polymorphisms between relevant cardiometabolic traits and arterial stiffness. METHOD:The study population consisted of 2853 individuals (mean age 72 years, 40% men) from the population-based Malmö Diet and Cancer study, Sweden. Carotid-femoral pulse wave velocity, a marker of arterial stiffness, was measured with Sphygmocor. Mendelian randomization analyses were performed using the two-stage least square regression and multivariate inverse-variance weighted methods. RESULTS:There were positive associations between arterial stiffness and genetic risk scores for type 2 diabetes (β = 0.03, P = 0.04) and fasting plasma glucose (β = 0.03, P = 0.03), but not for systolic blood pressure, body mass index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides. Multivariate inverse-variance weighted methods confirmed the significant positive association for fasting plasma glucose β coefficients (P = 0.006), but not for type 2 diabetes β coefficients (P = 0.88). CONCLUSION:Genetically elevated fasting plasma glucose, but not genetically elevated risk of type 2 diabetes, was associated with arterial stiffness suggesting a causal stiffening effect of glycemia on the arterial wall, independently of type 2 diabetes.

SUBMITTER: Gottsater M

PROVIDER: S-EPMC5861999 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveTo identify long-term fasting blood glucose trajectories and to assess the association between the trajectories and the risk of arterial stiffness in individuals without diabetes.MethodsWe enrolled 16,454 non-diabetic participants from Kailuan cohort. Fasting blood glucose concentrations were measured in 2006, 2008, and 2010 survey. Brachial-ankle pulse wave velocities were measured during 2011 to 2016. Multivariate regression model was used to estimate the difference of brachial-ankle pulse wave velocity levels and logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95%CIs) of arterial stiffness risk, according to the fasting blood glucose trajectories.ResultsWe identified five distinct fasting blood glucose trajectories and each of the trajectories was labeled according to its range and change over 2006-2010 survey: elevated-stable pattern (5.0% of participants), elevated-decreasing pattern (6.6%), moderate-increasing pattern (10.9%), moderate-stable pattern (59.3%), and low-stable pattern (18.2%). After adjustment for potential confounders, individuals with elevated-stable pattern had a 42.6 cm/s (95%CI: 24.7 to 60.6 cm/s) higher brachial-ankle pulse wave velocity level and a 37% (OR 1.37, 95%CI: 1.14 to 1.66) higher arterial stiffness risk, and individuals with moderate-increasing pattern had a 19.6 cm/s (95%CI: 6.9 to 32.3 cm/s) higher brachial-ankle pulse wave velocity level and a 17% (OR 1.17, 95%CI: 1.03 to 1.33) higher arterial stiffness risk, related to individuals with moderate-stable pattern. We did not find significant associations of the elevated-decreasing or low-stable patterns with arterial stiffness. Consistently, the cumulative average, variability, and increased rate of fasting blood glucose during 2006-2010 survey were significantly associated with the arterial stiffness risk.ConclusionDiscrete fasting blood glucose trajectories were associated with the arterial stiffness risk in non-diabetic individuals.

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A genetic risk score for fasting plasma glucose is independently associated with arterial stiffness: a Mendelian randomization study.

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