Complex association of serum alanine aminotransferase with the risk of future cardiovascular disease in type 2 diabetes.
We aimed to determine the prospective association between baseline serum levels of alanine aminotransferase (ALT) and the incident cardiovascular disease (CVD) in people with type 2 diabetes.



In an open cohort setting, people with type 2 diabetes were followed for their first ever CVD presentation from 1995 to 2015. Statistical methods included Cox regression analysis for reporting of hazard ratios (HRs), artificial neural network modelings, and risk reclassification analyses.



We found a nearly constant CVD hazard with baseline serum ALT levels below the 30 IU/L mark, whereas baseline serum ALT levels ≥ 30 IU/L remained an independent predictor of lower CVD rates in patients with type 2 diabetes in the final multivariate Cox proportional hazards regression model (HR: 0.204, 95%CI [0.060-0.689], pfor trendvalue = 0.006). Age, male gender and fasting plasma insulin levels independently predicted baseline serum ALT ≥ 30 IU/L among the population cohort. Augmentation of serum ALT into the weighted Framingham risk score resulted in a considerable net reclassification improvement (NRI) of coronary heart disease (CHD) risk prediction in the study population (NRI = 9.05% (8.01%-10.22%), p value < 0.05).



Serum ALT could successfully reclassify about 9% of the population with type 2 diabetes across the CHD-affected and CHD-free categories. Overall, our findings demonstrate a complex and nonlinear relationship for the risk of future CVD by baseline serum ALT levels in patients with type 2 diabetes. Further studies are warranted to confirm whether this complex association could be translated into a clearly visible U or J-shaped figure.
Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Mohsen
M
Afarideh
Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Student's Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Zahra
Z
Aryan
Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Alireza
A
Ghajar
Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Sina
S
Noshad
Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Manouchehr
M
Nakhjavani
The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York City, New York, United States.
Usman
U
Baber
Division of Endocrinology, Diabetes, and Bone Disease, Icahn School of Medicine at Mount Sinai, New York City, New York, United States.
Jeffrey I
JI
Mechanick
Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: esteghamati@tums.ac.ir.
Alireza
A
Esteghamati
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000150:complications; D003430:Cross-Sectional Studies; D048909:Diabetes Complications / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000175:diagnosis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016571:Neural Networks, Computer; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000150:complications; D010045:Outpatients; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
D000410:Alanine Transaminase
Cardiovascular disease; Non-alcoholic fatty liver disease; Serum alanine aminotransferase; Type 2 diabetes