Table 3.
Risk factors for severe liver disease in UK Biobank participants of European descent with type 2 diabetes (n = 22,812).
| Variable | HR (95% CI) | p value | aHR (95% CI) | p value |
|---|---|---|---|---|
| Age, years | 1.03 (1.02–1.05) | <0.001 | 1.01 (0.98–1.05) | 0.39 |
| Male sex | 1.76 (1.35–2.31) | <0.001 | 0.49 (0.26–0.94) | 0.031 |
| Family history of diabetes | 0.76 (0.60–0.98) | 0.031 | 0.74 (0.50–1.10) | 0.13 |
| Duration of diabetes, years | 1.01 (0.99–1.03) | 0.18 | 1.00 (0.97–1.03) | 0.97 |
| Comorbidities | ||||
| Hypertension | 1.44 (1.07–1.93) | 0.016 | 0.70 (0.42–1.18) | 0.18 |
| Dyslipidaemia | 0.89 (0.67–1.18) | 0.42 | ||
| BMI ≥30 kg/m2 | 1.84 (1.42–2.38) | <0.001 | 1.02 (0.64–1.64) | 0.93 |
| Waist circumference ≥94/80 cm | 2.80 (1.69–4.64) | <0.001 | 1.19 (0.49–2.92) | 0.70 |
| Cardiovascular disease | 1.94 (1.52–2.49) | <0.001 | 1.86 (1.23–2.79) | 0.003 |
| Lifestyle | ||||
| Low–moderate alcohol intake∗ | 0.71 (0.53–0.94) | 0.018 | 0.80 (0.49–1.31) | 0.38 |
| Excessive alcohol intake∗ | 1.63 (1.19–2.23) | 0.003 | 1.59 (0.93–2.71) | 0.091 |
| Current smoking status | 1.13 (0.79–1.63) | 0.51 | ||
| Physical activity ≥150/75 min/week | 1.00 (0.83–1.21) | 0.99 | ||
| Clinical chemistry | ||||
| HbA1c, mmol/mol | 1.00 (0.99–1.01) | 0.74 | ||
| ALT >30/19 U/L | 2.26 (1.76–2.90) | <0.001 | 1.37 (0.83–2.24) | 0.22 |
| AST >30/19 U/L | 5.18 (4.09–6.55) | <0.001 | 4.85 (2.76–8.54) | <0.001 |
| Albumin, per 0.5 g/dl decrease | 2.45 (2.01–2.99) | <0.001 | 2.39 (1.76–3.24) | <0.001 |
| Platelet count, per 10∗109/L decrease | 1.16 (1.13–1.18) | <0.001 | 1.12 (1.09–1.16) | <0.001 |
| eGFR <60 ml/min/1.73 m2 | 1.68 (1.12–2.51) | 0.012 | 1.22 (0.66–2.25) | 0.52 |
| Microalbuminuria | 1.70 (1.23–2.35) | 0.001 | 1.55 (1.04–2.30) | 0.03 |
| Macroalbuminuria | 1.37 (0.67–2.79) | 0.38 | ||
| Genetic risk factors | ||||
| PNPLA3 rs738409 genotype | ||||
| Additive model | 1.92 (1.61–2.30) | <0.001 | 1.67 (1.27–2.18) | <0.001 |
| Recessive model | 3.47 (2.49–4.84) | <0.001 | 2.32 (1.36–3.96)† | 0.002 |
| TM6SF2 rs58542926 genotype | ||||
| Additive model | 1.69 (1.32–2.17) | <0.001 | 1.63 (1.12–2.39) | 0.011 |
| Recessive model | 3.59 (1.70–7.62) | <0.001 | 4.33 (1.74–10.80)† | 0.002 |
| MBOAT7 rs641738 genotype | ||||
| Additive model | 1.09 (0.92–1.30) | 0.30 | ||
| Recessive model | 1.05 (0.78–1.42) | 0.75 | ||
| GCKR rs1260326 genotype | ||||
| Additive model | 1.04 (0.87–1.24) | 0.67 | ||
| Recessive model | 1.12 (0.80–1.56) | 0.52 | ||
| HSD17B13 rs72613567 genotype | ||||
| Additive model | 0.74 (0.60–0.91) | 0.004 | 0.74 (0.54–1.03) | 0.076 |
| Recessive model | 0.66 (0.38–1.13) | 0.13 | ||
| Drugs | ||||
| Metformin | 1.40 (1.10–1.78) | 0.006 | 1.46 (0.96–2.23) | 0.076 |
| Thiazolidinediones | 1.51 (1.04–2.20) | 0.03 | 1.48 (0.82–2.67) | 0.19 |
| Sulfonylureas | 1.40 (1.07–1.83) | 0.014 | 1.32 (0.87–1.99) | 0.19 |
| Insulin | 0.83 (0.61–1.14) | 0.26 | ||
| Statins | 0.91 (0.70–1.17) | 0.45 | ||
HRs with 95% CIs were calculated by Cox proportional hazards models. Age, sex, BMI, alcohol intake, duration of diabetes, and all predictor variables with a value of p <0.05 in the univariate model were included in the multivariate model.
aHR, adjusted HR; ALT, alanine aminotransferase; AST, aspartate aminotransferase; eGFR, estimated glomerular filtration rate; HbA1c, glycated haemoglobin; HR, hazard ratio.
∗
Low–moderate (<20/30 g/day) and excessive (≥20/30 g/day) alcohol intake tested against abstainers.
†
aHR calculated assuming recessive model instead of additive model.