Fig. 1Liver stiffness (kPa) distribution based on patatin like phospholipase domain containing 3 (PNPLA3) genotypes. Columns indicate medians, error bars interquartile ranges.
Fig. 2Liver stiffness (kPa) distribution among patatin like phospholipase domain containing 3 (PNPLA3) genotypes among 17β-hydroxysteroid-dehydrogenase type 13 (HSD17B13) (A) wild type and (B) mutated carriers. Columns indicate medians, error bars interquartile ranges. HSD17B13 T/T (wild type), HSD17B13 TA/* (heterozygous and/or homozygous “A” insertional mutation).
Fig. 3Predicted values of liver stiffness (LS) (kPa), based on patatin like phospholipase domain containing 3 (PNPLA3) genotype and body mass index (BMI). Error bars indicate 95% confidence intervals. The upper horizontal dotted line indicates LS value suggestive of cirrhosis, the lower one the value suggestive of absent or minimal fibrosis.
Table 1Main demographic and clinical characteristics of type 2 diabetes mellitus patients (n=328)
Variable |
Value |
Sex, male/female |
243 (74)/85 (26) |
Age, yr |
65 (58–71) |
Age at diagnosis of diabetes, yr |
55 (49–61) |
Diabetes duration, yr |
9 (4–14) |
Body mass index, kg/m2
|
27 (25–29) |
Waist circumference, cm |
98 (92–103) |
Female |
95 (90–100) |
Male |
98 (93–104) |
Steatosis grade (ultrasound)a
|
|
Absent |
17 (5) |
Grade 1 |
153 (47) |
Grade 2 |
96 (29) |
Grade 3 |
60 (18) |
Controlled attenuation parameter, dB/ma
|
248 (221–283) |
<236 |
133 (40.8) |
≥236–269 |
73 (22.4) |
≥270–301 |
64 (19.6) |
≥302 |
56 (17.2) |
Liver stiffness, kPa |
6.1 (4.9–8.6) |
<5.9 |
147 (44.8) |
≥5.9–7.9 |
87 (26.5) |
≥7.9 |
94 (28.7) |
Total cholesterol, mg/dL |
171 (150–191) |
HDL-C, mg/dL |
46 (39–57) |
Triglycerides, mg/dL |
119 (87–168) |
Aspartate aminotransferase, IU/L |
18 (15–23) |
Alanine aminotransferase, IU/L |
21 (15–30) |
Gamma glutamyltranspeptidase, IU/L |
23 (16–36) |
Platelet count, ×109/L |
236 (201–283) |
Fasting glucose, mg/dL |
134 (113–163) |
Albumin, g/L |
40.4 (38.4–42.5) |
HbA1c, mmol/mol |
55 (48–64) |
NAFLD score, unit |
−0.515 (−1.263 to 0.246) |
Significant fibrosis unlikely |
61 (19) |
Indeterminate |
223 (68) |
Significant fibrosis likely |
44 (13) |
FIB-4, unit |
1.09 (0.86–1.47) |
Significant fibrosis unlikely |
218 (66) |
Indeterminate |
102 (31) |
Significant fibrosis likely |
8 (2) |
Table 2Univariate analysis of factors associated with significant liver fibrosis defined as liver stiffness ≥7.9 kPa
Variable |
LS <7.9 kPa (n=234) |
LS ≥7.9 kPa (n=94) |
P value |
Male sex |
179 (24) |
64 (68) |
0.126 |
Age, yr |
64 (58–71) |
66 (58–71) |
0.877 |
Age at diagnosis of diabetes, yr |
54 (47–61) |
56 (50–61) |
0.132 |
Diabetes duration, yr |
10 (5–15) |
8 (3–12) |
0.126 |
Body mass index, kg/m2
|
26.6 (24.5–29.0) |
28.0 (26.4–30.4) |
<0.001 |
Waist circumference, cm |
97 (90–101) |
100 (95–107) |
0.004 |
Female (n=85) |
94 (90–99) |
98 (90–103) |
0.153 |
Male (n=179) |
98 (92–103) |
100 (95–107) |
0.008 |
Steatosis grade (ultrasound)a
|
|
|
|
Absent |
14 (6) |
3 (3) |
|
Grade 1 |
122 (53) |
31 (33) |
|
Grade 2 |
62 (27) |
34 (36) |
|
Grade 3 |
34 (15) |
26 (28) |
0.002 |
CAP, dB/m |
242 (219–280) |
266 (228–300) |
0.022 |
Total cholesterol, mg/dL |
170 (150–191) |
172 (148–196) |
0.865 |
HDL-C, mg/dL |
47 (39–57) |
44 (38–55) |
0.171 |
Triglycerides, mg/dL |
118 (81–153) |
122 (98–194) |
0.006 |
Aspartate aminotransferase, IU/L |
17 (15–21) |
22 (16–35) |
0.001 |
>Upper normal limit |
6 (3) |
18 (19) |
<0.001 |
Alanine aminotransferase, IU/L |
20 (15–27) |
25 (18–46) |
<0.001 |
>Upper normal limit |
22 (9) |
29 (31) |
<0.001 |
Gamma glutamyltranspeptidase, IU/L |
21 (16–31) |
30 (17–44) |
0.001 |
>Upper normal limit |
20 (9) |
17 (18) |
0.020 |
Platelet count, ×109/L |
237 (201–284) |
236 (201–284) |
0.887 |
Fasting glucose, mg/dL |
134 (113–160) |
130 (109–168) |
0.796 |
Albumin, g/L |
40.4 (38.3–42.5) |
40.4 (38.7–42.5) |
0.913 |
HbA1c, mmol/mol |
56 (48–65) |
54 (48–60) |
0.259 |
NAFLD score, unit |
−0.531 (–1.351 to 0.271) |
−0.447 (–0.861 to 0.092) |
0.368 |
FIB-4, unit |
1.07 (0.83–1.4) |
1.18 (0.9–1.65) |
0.048 |
Table 3Genotype and allele frequencies of the genes of interest
PNPLA3 (n=328) |
HSD17B13 (n=328) |
C/C |
154 (0.47) |
T/T |
223 (0.68) |
C/G |
139 (0.42) |
T/TA |
90 (0.27) |
G/G |
35 (0.11) |
TA/TA |
15 (0.05) |
G/*
|
174 (0.53) |
TA/*
|
105 (0.32) |
C |
447 (0.68) |
T |
536 (0.82) |
G |
209 (0.32) |
TA |
120 (0.18) |
HWE |
0.66 |
HWE |
0.14 |