Nonalcoholic Fatty Liver Disease Is Independently Associated With an Increased Incidence of Cardiovascular Events in Type 2 Diabetic Patients
- Giovanni Targher, MD12,
- Lorenzo Bertolini, MD1,
- Stefano Rodella, MD3,
- Roberto Tessari, MD1,
- Luciano Zenari, MD1,
- Giuseppe Lippi, MD4 and
- Guido Arcaro, MD1
- 1Unit of Internal Medicine and Diabetes, “Sacro Cuore” Hospital of Negrar, Negrar, Italy
- 2Section of Endocrinology, Biomedical and Surgical Sciences, University Hospital of Verona, Verona, Italy
- 3Department of Radiology, “Sacro Cuore” Hospital of Negrar, Negrar, Italy
- 4Section of Clinical Chemistry, Biomedical and Morphological Sciences, University Hospital of Verona, Verona, Italy
- Address correspondence and reprint requests to Dr. Giovanni Targher, Endocrinology and Metabolic Diseases, Ospedale Civile Magglore, Piazzale Stefani, 1, 37126 Verona, Italy. E-mail: giovanni.targher{at}univr.it
Recent data suggest that the presence of nonalcoholic fatty liver disease (NAFLD) in type 2 diabetes may be linked to increased cardiovascular disease (CVD) independent of components of the metabolic syndrome (1–3), although this hypothesis needs verification in larger studies. We assessed whether NAFLD, as diagnosed by ultrasound, predicts the risk of incident CVD events in a large cohort of type 2 diabetic adults.
RESEARCH DESIGN AND METHODS
Study subjects were participants in the Valpolicella Heart Diabetes Study (1). Briefly, we enrolled all of the type 2 diabetic outpatients (n = 2,103) who regularly attended our clinic in the period January–December 2000 after excluding those who had manifest CVD and/or secondary causes of chronic liver disease (alcohol abuse, viral infection, or medications). The local ethics committee approved the study. All participants provided written informed consent.
During 6.5 years of follow-up (through December 2006; follow-up range: 5–84 months), 384 participants subsequently developed CVD events (myocardial infarction, ischemic stroke, coronary revascularization, or cardiovascular death), whereas 1,719 patients remained free of diagnosed CVD. These events were ascertained by patient history, chart review, autopsy reports, and family contact (1).
Plasma liver enzymes, A1C, and other biochemical blood measurements were determined by standard procedures. At baseline, most participants (∼86%) had normal liver enzymes (reference ranges for aminotransferases were 10–35 and 10–50 units/l for female and male subjects, respectively) and were abstainers (77%) or drank minimally (13%); only 10% of participants …
