Higher Plasma Methylglyoxal Levels are Associated with Incident Cardiovascular Disease in Individuals with Type 1 Diabetes: a 12-Year Follow-Up Study

Methylglyoxal (MGO), a major precursor for advanced glycation endproducts (AGEs), 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. We recorded fatal and non-fatal CVD over a median follow-up of 12.3 years (interquartile range 7.6-12.5). Data were analyzed with Cox regression, with adjustment for sex, age, HbA1c, DN, diabetes duration, smoking, systolic blood pressure, anti-hypertensive medication and BMI. During follow-up, 73 individuals suffered at least one CVD event (36 fatal and 53 non-fatal events). Higher MGO levels were associated with total, fatal and nonfatal incident CVD (HRs: 1.47; 95%CI: 1.13-1.91, 1.42; 95%CI: 1.01-1.99 and 1.46; 95%CI: 1.08-1.98, respectively). We observed a similar trend for total mortality (HR: 1.24; 95%CI: 0.99-1.56). This study shows, for the first time, that plasma MGO levels are associated with cardiovascular events in individuals with type 1 diabetes. MGO may explain the increased risk, at least in part, for CVD in type 1 diabetes.