TY - JOUR
T1 - Insulin resistance and central obesity determine hepatic steatosis and explain cardiovascular risk in steatotic liver disease
AU - Semmler, G
AU - Balcar, L
AU - Wernly, S
AU - Völkerer, A
AU - Semmler, L
AU - Hauptmann, L
AU - Wernly, B
AU - Aigner, E
AU - Niederseer, D
AU - Datz, C
N1 - Lehr-KH Oberndorf;
S und B Wernly: Department of Internal Medicine, General Hospital Oberndorf, Teaching
Hospital of the Paracelsus Medical University Salzburg, Salzburg, Austria;
Aigner: First Department of Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria,
PY - 2023/9/29
Y1 - 2023/9/29
N2 - Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has recently been proposed to replace non-alcoholic fatty liver disease and focus on patients with progressive disease due to the presence of metabolic dysfunction. However, it is unclear whether the new definition actually identifies patients with hepatic steatosis at increased cardiovascular risk. Methods: A total of 4,286 asymptomatic subjects from the SAKKOPI study aged 45-80 years undergoing screening colonoscopy were analyzed. Steatosis was diagnosed by abdominal ultrasound. MASLD was diagnosed according to the recent expert consensus. Insulin resistance was assessed by homeostasis model assessment-insulin resistance score (HOMA-IR) (cutoff: >= 2.5), subclinical inflammation was estimated by ferritin/CRP/uric acid, and cardiovascular risk was assessed using SCORE2/ASCVD. Results: Mean age was 59.4 +/- 8.5 years, 51.6% were male; mean BMI was 27.0 +/- 4.5 kg/m(2), 9.2% had type 2 diabetes mellitus. In total, 1,903 (44.4%) were diagnosed with hepatic steatosis and were characterized by more severe metabolic dysfunction including insulin resistance (47.1% vs. 12.2%, p < 0.001) and central obesity (waist circumference >= 102/88 cm, 71.8% vs. 37.1%, p < 0.001). This translated into higher (subclinical) inflammation (ferritin 153 vs. 95 mg/dL, p < 0.001, uric acid 6.3 mg/dL vs. 5.2 mg/dL, p < 0.001) and 10-year cardiovascular risk (SCORE2 7.8 points vs. 5.1 points, p < 0.001, ASCVD 17.9 points vs. 10.8 points, p < 0.001). 99.0% of subjects with steatosis met the MASLD definition, 95.4% met the MAFLD definition, and 53.6% met the definition of metabolic syndrome, while 95.4% of subjects without steatosis also met the MASLD criteria for metabolic dysfunction compared to 69.0% and 17.4% who met the MAFLD and metabolic syndrome criteria, respectively. Forward stepwise regression indicated that waist circumference, HOMA-IR, and triglycerides were most relevant in explaining the presence of hepatic steatosis across all subgroups of increasing metabolic dysfunction. At the same time, hepatic steatosis was not associated with cardiovascular risk in the overall cohort (SCORE2: B = 0.060, 95% CI: -0.193-0.314, and p = 0.642) and in patients with metabolic dysfunction after adjusting for age, sex, and these three metabolic dysfunction components. Conclusion: Although hepatic steatosis is associated with increased central obesity and insulin resistance, metabolic dysfunction per se rather than hepatic steatosis explains cardiovascular risk in these patients.
AB - Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has recently been proposed to replace non-alcoholic fatty liver disease and focus on patients with progressive disease due to the presence of metabolic dysfunction. However, it is unclear whether the new definition actually identifies patients with hepatic steatosis at increased cardiovascular risk. Methods: A total of 4,286 asymptomatic subjects from the SAKKOPI study aged 45-80 years undergoing screening colonoscopy were analyzed. Steatosis was diagnosed by abdominal ultrasound. MASLD was diagnosed according to the recent expert consensus. Insulin resistance was assessed by homeostasis model assessment-insulin resistance score (HOMA-IR) (cutoff: >= 2.5), subclinical inflammation was estimated by ferritin/CRP/uric acid, and cardiovascular risk was assessed using SCORE2/ASCVD. Results: Mean age was 59.4 +/- 8.5 years, 51.6% were male; mean BMI was 27.0 +/- 4.5 kg/m(2), 9.2% had type 2 diabetes mellitus. In total, 1,903 (44.4%) were diagnosed with hepatic steatosis and were characterized by more severe metabolic dysfunction including insulin resistance (47.1% vs. 12.2%, p < 0.001) and central obesity (waist circumference >= 102/88 cm, 71.8% vs. 37.1%, p < 0.001). This translated into higher (subclinical) inflammation (ferritin 153 vs. 95 mg/dL, p < 0.001, uric acid 6.3 mg/dL vs. 5.2 mg/dL, p < 0.001) and 10-year cardiovascular risk (SCORE2 7.8 points vs. 5.1 points, p < 0.001, ASCVD 17.9 points vs. 10.8 points, p < 0.001). 99.0% of subjects with steatosis met the MASLD definition, 95.4% met the MAFLD definition, and 53.6% met the definition of metabolic syndrome, while 95.4% of subjects without steatosis also met the MASLD criteria for metabolic dysfunction compared to 69.0% and 17.4% who met the MAFLD and metabolic syndrome criteria, respectively. Forward stepwise regression indicated that waist circumference, HOMA-IR, and triglycerides were most relevant in explaining the presence of hepatic steatosis across all subgroups of increasing metabolic dysfunction. At the same time, hepatic steatosis was not associated with cardiovascular risk in the overall cohort (SCORE2: B = 0.060, 95% CI: -0.193-0.314, and p = 0.642) and in patients with metabolic dysfunction after adjusting for age, sex, and these three metabolic dysfunction components. Conclusion: Although hepatic steatosis is associated with increased central obesity and insulin resistance, metabolic dysfunction per se rather than hepatic steatosis explains cardiovascular risk in these patients.
KW - Humans
KW - Male
KW - Middle Aged
KW - Aged
KW - Female
KW - Insulin Resistance
KW - Metabolic Syndrome/complications
KW - Obesity, Abdominal/complications
KW - Diabetes Mellitus, Type 2/complications
KW - Uric Acid
KW - Cardiovascular Diseases/diagnosis
KW - Risk Factors
KW - Obesity/complications
KW - Non-alcoholic Fatty Liver Disease/complications
KW - Heart Disease Risk Factors
KW - Inflammation/complications
KW - Ferritins
U2 - 10.3389/fendo.2023.1244405
DO - 10.3389/fendo.2023.1244405
M3 - Original Article
C2 - 37842290
SN - 1664-2392
VL - 14
SP - 1244405
JO - FRONTIERS IN ENDOCRINOLOGY
JF - FRONTIERS IN ENDOCRINOLOGY
M1 - 1244405
ER -