Higher Plasma Methylglyoxal Levels Are Associated With Incident Cardiovascular Disease in Individuals With Type 1 Diabetes: A 12-Year Follow-up Study

TY - JOUR

T1 - Higher Plasma Methylglyoxal Levels Are Associated With Incident Cardiovascular Disease in Individuals With Type 1 Diabetes

T2 - A 12-Year Follow-up Study

AU - Hanssen, Nordin M.J.

AU - Scheijen, Jean L.J.M.

AU - Jorsal, Anders

AU - Parving, Hans Henrik

AU - Tarnow, Lise

AU - Rossing, Peter

AU - Stehouwer, Coen D.A.

AU - Schalkwijk, Casper G.

PY - 2017/8

Y1 - 2017/8

N2 - Methylglyoxal (MGO), a major precursor for advanced glycation end products, is increased in diabetes. In diabetic rodents, inhibition of MGO prevents cardiovascular disease (CVD). Whether plasma MGO levels are associated with incident CVD in people with type 1 diabetes is unknown. We included 159 individuals with persistent normoalbuminuria and 162 individuals with diabetic nephropathy (DN) from the outpatient clinic at Steno Diabetes Center.We measured MGO at baseline and recorded fatal and nonfatal CVD over a median follow-up of 12.3 years (interquartile range 7.6-12.5 years). Data were analyzed by Cox regression, with adjustment for sex, age, HbA1c, DN, diabetes duration, smoking, systolic blood pressure, antihypertensive medication, and BMI. During follow-up, 73 individuals suffered at least one CVD event (36 fatal and 53 nonfatal). Higher MGO levels were associated with total, fatal, and nonfatal incident CVD (hazard ratios [HRs] 1.47 [95% CI 1.13-1.91], 1.42 [1.01-1.99], and 1.46 [1.08-1.98], respectively). We observed a similar trend for total mortality (HR 1.24 [0.99-1.56]). This study shows for the first time in our knowledge that plasma MGO levels are associated with cardiovascular events in individuals with type 1 diabetes. MGO may explain, at least in part, the increased risk for CVD in type 1 diabetes.

AB - Methylglyoxal (MGO), a major precursor for advanced glycation end products, is increased in diabetes. In diabetic rodents, inhibition of MGO prevents cardiovascular disease (CVD). Whether plasma MGO levels are associated with incident CVD in people with type 1 diabetes is unknown. We included 159 individuals with persistent normoalbuminuria and 162 individuals with diabetic nephropathy (DN) from the outpatient clinic at Steno Diabetes Center.We measured MGO at baseline and recorded fatal and nonfatal CVD over a median follow-up of 12.3 years (interquartile range 7.6-12.5 years). Data were analyzed by Cox regression, with adjustment for sex, age, HbA1c, DN, diabetes duration, smoking, systolic blood pressure, antihypertensive medication, and BMI. During follow-up, 73 individuals suffered at least one CVD event (36 fatal and 53 nonfatal). Higher MGO levels were associated with total, fatal, and nonfatal incident CVD (hazard ratios [HRs] 1.47 [95% CI 1.13-1.91], 1.42 [1.01-1.99], and 1.46 [1.08-1.98], respectively). We observed a similar trend for total mortality (HR 1.24 [0.99-1.56]). This study shows for the first time in our knowledge that plasma MGO levels are associated with cardiovascular events in individuals with type 1 diabetes. MGO may explain, at least in part, the increased risk for CVD in type 1 diabetes.

U2 - 10.2337/db16-1578

DO - 10.2337/db16-1578

M3 - Journal article

C2 - 28588100

AN - SCOPUS:85025622398

SN - 0012-1797

VL - 66

SP - 2278

EP - 2283

JO - Diabetes

JF - Diabetes

IS - 8

ER -