Methylglyoxal Adducts Are Prognostic Biomarkers for Diabetic Kidney Disease in Patients With Type 1 Diabetes.

More than 30% of patients with type 1 diabetes develop diabetic kidney disease (DKD), which significantly increases mortality risk. The Diabetes Control and Complications Trial (DCCT) and follow-up study, Epidemiology of Diabetes Interventions and Complications (EDIC), established that glycemic control measured by HbA1c predicts DKD risk. However, the continued high incidence of DKD reinforces the urgent need for additional biomarkers to supplement HbA1c. Here, we assessed biomarkers induced by methylglyoxal (MG), a metabolic by-product that forms covalent adducts on DNA, RNA, and proteins, called MG adducts. Urinary MG adducts were measured in samples from patients with type 1 diabetes enrolled in DCCT/EDIC who did (case patients; n = 90) or did not (control patients; n = 117) develop DKD. Univariate and multivariable analyses revealed that measurements of MG adducts independently predict DKD before established DKD biomarkers such as glomerular filtration rate and albumin excretion rate. Elevated levels of MG adducts bestowed the greatest risk of developing DKD in a multivariable model that included HbA1c and other clinical covariates. Our work establishes a novel class of biomarkers to predict DKD risk and suggests that inclusion of MG adducts may be a valuable tool to improve existing predictors of complications like DKD prior to overt disease, and to aid in identifying at-risk individuals and personalized risk management.

An emerging trend of rapid increase of leukemia but not all cancers in the aging population in the United States.

The "baby boomers" born in 1946-1964 in the United States (U.S.) started to reach the age of 65 in 2011, rapidly accelerating U.S. population aging. There are great public concerns about its impact on health care with anticipation of rising cancer incidences. We examined the incidences and deaths of leukemia and overall cancer in the U.S. from 1998 to 2018. The acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) incidences remained constant prior to 2011 but have climbed up substantially since then, and the chronic lymphocytic leukemia (CLL) incidence has increased continuously since 1998. The significant increase of myeloid leukemia and CLL incidences was strongly correlated with the U.S. population aging. The incidence of all cancers was increased in correlation with a small increase in aging population prior to 2011, but surprisingly has changed marginally since 2011, which was not significantly correlated with the accelerated population aging. We observed the most substantial decline of deaths with CML, whereas AML deaths continued to rise in the past 20 years. In conclusion, the overall cancer incidence was not increased as fast as previously feared with aging Americans; however, the incidences of myeloid leukemia and CLL significantly outpaced that of all cancers.