Key result
Medium-to-high grade hepatic steatosis is linked to ~6% lower insulin sensitivity in severe obesity and T2D.
Why the study?
Obesity, NAFLD, and insulin resistance are highly correlated, but this relationship is not fully elucidated.
Is hepatic steatosis or fibrosis associated with insulin sensitivity in patients with severe obesity and T2DM?
Cross-Sectional (n=100)
No
Is hepatic steatosis or fibrosis associated with insulin sensitivity in patients with severe obesity and T2DM?
Mean Difference: 5.9 (95% CI 2.2–9.6)
Absolute Event Rate: 20.4% vs 26.3%
p-value: p=0.002
In patients with severe obesity and T2DM, hepatic steatosis, but not liver fibrosis, is inversely associated with measures of insulin sensitivity.
Lower hepatic insulin sensitivity with steatosis warrants no practice change; leaves open causal role in obese T2D.
BackgroundObesity, non-alcoholic fatty liver disease (NAFLD) and insulin resistance are three pathological conditions highly correlated, but this relationship is not fully elucidated. Hence, we aimed to assess the association of hepatic steatosis and fibrosis with different measures of insulin sensitivity in patients with severe obesity and type 2 diabetes mellitus (T2DM).MethodsA cross-sectional study (Oseberg trial) including patients with T2DM referred for bariatric surgery at Vestfold Hospital Trust, Norway. Magnetic resonance imaging (MRI) and the enhanced liver fibrosis (ELF) test was used for estimation of liver fat fraction (LFF) and degree of fibrosis, respectively. Oral and intravenous glucose tolerance tests were applied for estimation of insulin sensitivity (HOMA2S, Matsuda ISI and MinMod SI).ResultsA total of 100 patients (mean [SD] age 47.5 [9.7] years, 65% women, BMI 42.0 [5.3] kg/m² and 98% with metabolic syndrome) were included in the analyses. The mean (SD) LFF in the total population was 19.1 (11.5), and the mean (SD) ELF score was 8.46 (0.84), a value representing moderate fibrosis. LFF was inversely associated with HOMA2S and Matsuda ISI, and both measures were significantly higher in the no or low-grade steatosis group compared with the medium-to-high grade steatosis group (mean difference [95% CI] 5.9 [2.2-9.6]%, Cohen’s d=0.75), and (0.7 [0.3-1.1], Cohen’s d=0.80, respectively). There was no association between LFF, as a categorical or continuous variable, and MinMod SI. The proportions of patients with none to mild fibrosis, moderate fibrosis and severe fibrosis were 14, 78 and 6%, respectively, and there were no significant associations between level of fibrosis and measures of insulin sensitivity. ConclusionsPatients with morbid obesity and T2DM demonstrated high levels of liver fat fraction, and we showed that hepatic steatosis, but not the degree of liver fibrosis, was associated with different measures of insulin sensitivity in patients with severe obesity and T2DM. Further, our results might indicate that the LFF is primarily associated with hepatic, and not peripheral insulin sensitivity. To improve the diagnosis of NAFLD and the prediction of its progression, more studies are needed to reveal the pathological mechanistic pathways involved in NAFLD and insulin sensitivity.Trial RegistrationClinicalTrials.gov:NCT01778738
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Seeberg et al. (2022) conducted a cross-sectional in Severe obesity and type 2 diabetes mellitus (n=100). Medium-to-high grade hepatic steatosis vs. No or low-grade hepatic steatosis was evaluated on Insulin sensitivity measured by HOMA2S (MD 5.9, 95% CI 2.2-9.6, p=0.002). Medium-to-high grade hepatic steatosis was associated with significantly lower hepatic insulin sensitivity (HOMA2S mean difference 5.9%) compared to no or low-grade steatosis in patients with severe obesity and type 2 diabetes.
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