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.
AU - SMART Study Grp
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, HbA(1c), 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 (hazard ratio 1.26 [95% CI 1.11-1.42]) 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, HbA(1c), 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 (hazard ratio 1.26 [95% CI 1.11-1.42]) 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.
KW - GLYCATION END-PRODUCTS
KW - FOLLOW-UP
KW - EPIC-NL
KW - COHORT
KW - EVENTS
KW - MICE
U2 - 10.2337/dc18-0159
DO - 10.2337/dc18-0159
M3 - Article
C2 - 29784769
SN - 0149-5992
VL - 41
SP - 1689
EP - 1695
JO - Diabetes Care
JF - Diabetes Care
IS - 8
ER -