Nonalcoholic Fatty Liver Disease and Risk of Future Cardiovascular Events Among Type 2 Diabetic Patients Giovanni Targher, Lorenzo Bertolini, Felice Poli, Stefano Rodella, et al. Giovanni Targher, Lorenzo Bertolini, Felice Poli, Stefano Rodella, et al. DIABETES, VOL. 54. DECEMBER 2005

BACKGROUDS Nonalcoholic fatty liver disease (NAFLD) Nonalcoholic fatty liver disease (NAFLD) –clinicopathologic syndrome –visceral obesity, dyslipidemia, insulin resistance, and type 2 diabetes metabolic syndrome predicts incident CVD metabolic syndrome predicts incident CVD NAFLD patients might portend a CVD risk NAFLD patients might portend a CVD risk

carotid artery wall thickness carotid artery wall thickness –patients with NAFLD > those without NAFLD –only a marker of early generalized atherosclerosis NAFLD is associated with increased risk of future CVD events ?? NAFLD is associated with increased risk of future CVD events ??

AIMS prospectively prospectively whether NAFLD predicts future CVD events whether NAFLD predicts future CVD events among type 2 diabetic individuals among type 2 diabetic individuals independent of metabolic syndrome features independent of metabolic syndrome features and other classical risk factors and other classical risk factors

METHODS Study subjects Study subjects –participants in the Valpolicella Heart Diabetes Study –all of the outpatients with type 2 diabetes (n = 2,103 ) –1 January 2000 ~ 31 December 2000 –free of diagnosed CVD –not abusing alcohol –not have other known causes of chronic liver disease –All participants were periodically seen (every 4-6 months)

an average of 5 years of follow-up an average of 5 years of follow-up case subjects : 248 participants case subjects : 248 participants –subsequently developed CVD control subjects : 496 participants control subjects : 496 participants –randomly selected in a 2:1 ratio –matched for age and sex CVD CVD –cardiovascular death –nonfatal ischemic stroke or CHD

Laboratory procedures and clinical measurements Plama LFT : AST, ALT, GGT Plama LFT : AST, ALT, GGT serology for hepatitis B or C : negative serology for hepatitis B or C : negative LDL cholesterol : Friedewald's equation LDL cholesterol : Friedewald's equation –LDG = Chol – HDL – TG/5 HbA1C HbA1C urinary albumin excretion rate urinary albumin excretion rate –the albumin-to-creatinine ratio BMI BMI –weight in kilograms by height in meters squared

Waist circumference Waist circumference Blood pressure Blood pressure alcohol consumption, lifestyle characteristics alcohol consumption, lifestyle characteristics –questionnaire Metabolic syndrome Metabolic syndrome –ATP III Hepatic ultrasound scanning Hepatic ultrasound scanning –Hepatic steatosis evidence of diffuse hyperechogenicity of liver relative to kidneys evidence of diffuse hyperechogenicity of liver relative to kidneys ultrasound beam attenuation, and poor visualization of intrahepatic structures ultrasound beam attenuation, and poor visualization of intrahepatic structures

Statistical analysis Statistical analysis

RESULTS 248 incident CVD events 248 incident CVD events –142 nonfatal CHD 101 myocardial infarction 101 myocardial infarction 41 CABG/ PCI 41 CABG/ PCI –29 nonfatal ischemic stroke –77 deaths from cardiovascular events

DISCUSSION biological mechanisms biological mechanisms –increased whole-body insulin resistance and dyslipidemia –increased oxidative stress and subclinical inflammation –Decreased plasma levels of adiponectin –abnormal lipoprotein metabolism Apolipoprotein B-100 synthesis ↓ Apolipoprotein B-100 synthesis ↓

limitation limitation –diagnosis of NAFLD ultrasonography ultrasonography exclusion of known etiologic factors of chronic liver disease exclusion of known etiologic factors of chronic liver disease –we cannot obviously exclude the possibility of a differential relationship between the broad spectrum of NAFLDs and CVD risk

CONCLUSION NAFLD with type 2 DM CVD risk CVD risk