Nonalcoholic Fatty Liver Disease and Risk of Future Cardiovascular Events Among Type 2 Diabetic Patients

Pathophysiology

¹Division of Internal Medicine and Diabetes Unity, “Sacro Cuore” Hospital of Negrar, Negrar, Verona, Italy
²Department of Radiology, “Sacro Cuore” Hospital of Negrar, Negrar, Verona, Italy

Address correspondence and reprint requests to Giovanni Targher, MD, Division of Internal Medicine and Diabetes Unit, Ospedale “Sacro Cuore –don G. Calabria,” Via Sempreboni, 5, 37024 Negrar (VR), Italy. E-mail: targher{at}sacrocuore.it

Article Figures & Tables

TABLE 1

Baseline characteristics of the study participants (n = 744)

Variables	Control subjects	Case subjects	P
n	496	248	—
Sex (% men)	62	62	NS*
Age (years)	65 ± 3	66 ± 4	NS*
BMI (kg/m²)	26 ± 3	29 ± 4	<0.001
Waist circumference (cm)	93 ± 13	101 ± 14	<0.001
Duration of diabetes (years)	13 ± 3	14 ± 3	NS
Oral hypoglycemic agents (%)	61.9	63.3	NS
Insulin treatment only (%)	12	14	NS
Current smokers (%)	20	22	NS
Systolic blood pressure (mmHg)	124 ± 13	131 ± 15	<0.001
Diastolic blood pressure (mmHg)	79 ± 12	83 ± 10	<0.001
A1C (%)	6.9 ± 0.8	7.2 ± 0.9	0.059
Triglycerides (mmol/l)	1.24 ± 0.6	1.62 ± 0.9	<0.001
HDL cholesterol (mmol/l)	1.39 ± 0.3	1.25 ± 0.4	<0.001
LDL cholesterol (mmol/l)	3.29 ± 0.4	3.27 ± 0.5	NS
AST (units/l)	20 ± 10	26 ± 12	<0.01
ALT (units/l)	23 ± 12	33 ± 14	<0.001
GGT (units/l)	27 ± 14	38 ± 16	<0.001
Microalbuminuria (%)	20	23	NS
ATP III–defined metabolic syndrome (%)	52	73	<0.001
NAFLD (%)	56	94	<0.001

Data are the means ± SD, unless otherwise indicated. Differences were assessed by the unpaired t test (for normally distributed variables) and by the χ² test (for categorical variables).
*
* Matched variables.

TABLE 2

Univariate and multivariate logistic regression analyses of factors associated with incident CVD events among type 2 diabetic patients

Variables	Univariate	Multivariate model 1	Multivariate model 2	Multivariate model 3
NAFLD
OR	1.91	1.9	1.84	1.53
95% CI	1.4–2.2	1.4–2.2	1.4–2.1	1.1–1.7
P values	0.001	0.001	0.001	0.02
ATP III–defined metabolic syndrome
OR	1.64	1.64	1.62	1.58
95% CI	1.3–2.5	1.3–2.3	1.3–2.1	1.3–2
P values	0.001	0.001	0.001	0.01
Age
OR	1.14	1.13	1.13	1.12
95% CI	1.07–1.16	1.07–1.14	1.07–1.14	1.06–1.14
P values	0.001	0.001	0.001	0.001
Sex
OR	1.50	1.48	1.46	1.46
95% CI	1.2–2	1.2–2	1.2–1.9	1.2–1.9
P values	0.001	0.001	0.001	0.001
Diabetes duration
OR	1.08	NS	NS	NS
95% CI	0.8–1.3	NS	NS	NS
P values	NS	NS	NS	NS
A1C
OR	1.51	1.46	NS	NS
95% CI	1.1–4.9	1.02–4.2	NS	NS
P values	0.02	0.05	NS	NS
Smoking status
OR	1.44	1.42	1.40	1.40
95% CI	1.1–2.0	1.1–2.0	1.1–1.9	1.1–1.9
P values	0.01	0.01	0.01	0.01
LDL cholesterol
OR	1.18	NS	NS	NS
95% CI	0.9–1.4	NS	NS	NS
P values	NS	NS	NS	NS
GGT
OR	1.42	1.40	1.27	NS
95% CI	1.1–2.0	1.1–1.9	1.05–1.7	NS
P values	0.001	0.001	0.01	NS
Use of medications
OR	1.0	NS	NS	NS
95% CI	0.7–1.2	NS	NS	NS
P values	NS	NS	NS	NS

Model 1: adjustment for age and sex; model 2: further adjustment for smoking history, diabetes duration, A1C, LDL cholesterol, GGT levels, and use of medications (i.e., hypoglycemic, antihypertensive, lipid-lowering, or antiplatelet drugs); model 3: additional adjustment for the presence of metabolic syndrome or NAFLD (for the first and second variables in the table) or additional adjustment for the presence of metabolic syndrome and NAFLD (for all other variables in the table).