TY - JOUR
T1 - Higher plasma methylglyoxal levels are associated with incident cardiovascular disease and mortality in individuals with type 2 diabetes
AU - Hanssen, Nordin M.J.
AU - Westerink, Jan
AU - Scheijen, Jean L.J.M.
AU - Van Der Graaf, Yolanda
AU - Stehouwer, Coen D.A.
AU - Schalkwijk, Casper G.
N1 - Funding Information:
Funding.N.M.J.H.issupportedbyaDr.E.Dekker grant from the Dutch Heart Foundation (2017T039) and a junior postdoctoral grant from the Dutch Diabetes Research Foundation (2017.81.005). Duality of Interest.Thisresearchwassupported by a European Foundation for the Study of Diabetes/Lilly program. No other potential conflicts of interest relevant to this article were reported. Author Contributions. N.M.J.H. analyzed data and wrote the manuscript. J.W. and Y.v.d.G. designed the study and wrote and edited the manuscript. J.L.J.M.S. measured plasma dicar-bonyls and edited the manuscript. C.D.A.S. wrote and edited the manuscript. C.G.S. was the principal investigator and wrote and edited the manuscript. C.G.S. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Publisher Copyright:
© 2018 by the American Diabetes Association.
PY - 2018/8/1
Y1 - 2018/8/1
N2 - OBJECTIVE: Methylglyoxal (MGO) is a reactive dicarbonyl compound and a potential key player in diabetic cardiovascular disease (CVD). Whether plasma MGO levels are associated with CVD in type 2 diabetes is unknown. RESEARCH DESIGN AND METHODS: We included 1,003 individuals (mean ± SD age 59.1 ± 10.5 years, 69.3% male, and 61.6% with prior CVD) with type 2 diabetes from the Second Manifestations of ARTerial disease cohort (SMART). We measured plasma MGO levels and two other dicarbonyls (glyoxal [GO] and 3-deoxyglucosone [3-DG]) at baseline with mass spectrometry. Median follow-up of CVD events was 8.6 years. Data were analyzed with Cox regression with adjustment for sex, age, smoking, systolic blood pressure, total cholesterol, HbA1c, BMI, prior CVD, and medication use. Hazard ratios are expressed per SD Ln-transformed dicarbonyl. RESULTS: A total of 287 individuals suffered from at least one CVD event(n = 194 fatal events, n = 146 myocardial infarctions, and n = 72 strokes); 346 individuals died, and 60 individuals underwent an amputation. Higher MGO levels were associated with total (hazardratio 1.26 [95%CI1.11-1.42]) and fatal(1.49 [1.30-1.71]) CVD and with all-cause mortality (1.25 [1.11-1.40]), myocardial infarction (1.22 [1.02-1.45]), and amputations (1.36 [1.05-1.76]). MGO levels were not apparently associated with stroke (1.03 [0.79-1.35]). Higher GO levels were significantly associated with fatal CVD (1.17 [1.00-1.37]) but not with other outcomes. 3-DG was not significantly associated with any of the outcomes. CONCLUSIONS: Plasma MGO and GO levels are associated with cardiovascular mortality in individuals with type 2 diabetes. Influencing dicaronyl levels may therefore be a target to reduce CVD in type 2 diabetes.
AB - OBJECTIVE: Methylglyoxal (MGO) is a reactive dicarbonyl compound and a potential key player in diabetic cardiovascular disease (CVD). Whether plasma MGO levels are associated with CVD in type 2 diabetes is unknown. RESEARCH DESIGN AND METHODS: We included 1,003 individuals (mean ± SD age 59.1 ± 10.5 years, 69.3% male, and 61.6% with prior CVD) with type 2 diabetes from the Second Manifestations of ARTerial disease cohort (SMART). We measured plasma MGO levels and two other dicarbonyls (glyoxal [GO] and 3-deoxyglucosone [3-DG]) at baseline with mass spectrometry. Median follow-up of CVD events was 8.6 years. Data were analyzed with Cox regression with adjustment for sex, age, smoking, systolic blood pressure, total cholesterol, HbA1c, BMI, prior CVD, and medication use. Hazard ratios are expressed per SD Ln-transformed dicarbonyl. RESULTS: A total of 287 individuals suffered from at least one CVD event(n = 194 fatal events, n = 146 myocardial infarctions, and n = 72 strokes); 346 individuals died, and 60 individuals underwent an amputation. Higher MGO levels were associated with total (hazardratio 1.26 [95%CI1.11-1.42]) and fatal(1.49 [1.30-1.71]) CVD and with all-cause mortality (1.25 [1.11-1.40]), myocardial infarction (1.22 [1.02-1.45]), and amputations (1.36 [1.05-1.76]). MGO levels were not apparently associated with stroke (1.03 [0.79-1.35]). Higher GO levels were significantly associated with fatal CVD (1.17 [1.00-1.37]) but not with other outcomes. 3-DG was not significantly associated with any of the outcomes. CONCLUSIONS: Plasma MGO and GO levels are associated with cardiovascular mortality in individuals with type 2 diabetes. Influencing dicaronyl levels may therefore be a target to reduce CVD in type 2 diabetes.
UR - http://www.scopus.com/inward/record.url?scp=85053860303&partnerID=8YFLogxK
U2 - 10.2337/dc18-0159
DO - 10.2337/dc18-0159
M3 - Article
C2 - 29784769
AN - SCOPUS:85053860303
SN - 0149-5992
VL - 41
SP - 1689
EP - 1695
JO - Diabetes Care
JF - Diabetes Care
IS - 8
ER -