TY - JOUR
T1 - Metabolic disturbances of non-alcoholic fatty liver resemble the alterations typical for type 2 diabetes
AU - Brouwers, Bram
AU - Schrauwen-Hinderling, Vera B.
AU - Jelenik, Tomas
AU - Gemmink, Anne
AU - Havekes, Bas
AU - Bruls, Yvonne
AU - Dahlmans, Dennis
AU - Roden, Michael
AU - Hesselink, Matthijs K. C.
AU - Schrauwen, Patrick
PY - 2017/8/1
Y1 - 2017/8/1
N2 - Non-alcoholic fatty liver (NAFL) is an independent risk factor for the development of type 2 diabetes (T2DM). We examined metabolic perturbations in patients with NAFL, patients with T2DM, and control (CON) subjects with normal intrahepatic lipid (IHL) content. A two-step (10 mU/m(2) /min; 40 mU/m(2)/min) hyperinsulinemic-euglycemic clamp was performed in 11 NAFL, 13 T2DM, and 11 CON subjects, all matched for BMI, and aerobic fitness. IHL content was measured using proton magnetic resonance spectroscopy. Because of high IHL content variability in T2DM patients, this group was separated into a high IHL content group (IHL >= 5.0%, T2DM+ NAFL) and a normal IHL content group (IHL <5.0%, T2DM-non-NAFL) for further analysis.IHL content was increased in NAFL and T2DM+ NAFL subjects (P <0.050 versus CON and T2DM-non-NAFL subjects). Adipose tissue insulin sensitivity index (Adipo-IRi) was higher in NAFL (P<0.050 versus CON and T2DM-non-NAFL subjects) and in T2DM+ NAFL subjects (P= 0.055 versus CON subjects, P<0.050 versus T2DM-non-NAFL subjects). Suppression of plasma-free fatty acids (P= 0.046) was lower in NAFL compared with CON subjects, with intermediate values for T2DM-non-NAFL, and T2DM+ NAFL subjects. Suppression of endogenous glucose production (EGP) and insulin-stimulated glucose disposal (Delta R-d) was comparable between NAFL, T2DM-non-NAFL, and T2DM+ NAFL subjects (all P> 0.05), and was lower in comparison with CON subjects (all P<0.01). Metabolic flexibility was lower in T2DM-non-NAFL subjects (P= 0.047) and NAFL subjects (P= 0.059) compared with CON subjects. Adipo-IRi (r= 0.652, P<0.001), hepatic insulin resistance index (HIRi) (r= 0.576, P= 0.001), and Delta R-d (r=-0.653, P<0.001) correlated with IHL content.Individuals with NAFL suffer from metabolic perturbations to a similar degree as T2DM patients. NAFL is an important feature leading to severe insulin resistance and should be viewed as a serious health threat for the development of T2DM.
AB - Non-alcoholic fatty liver (NAFL) is an independent risk factor for the development of type 2 diabetes (T2DM). We examined metabolic perturbations in patients with NAFL, patients with T2DM, and control (CON) subjects with normal intrahepatic lipid (IHL) content. A two-step (10 mU/m(2) /min; 40 mU/m(2)/min) hyperinsulinemic-euglycemic clamp was performed in 11 NAFL, 13 T2DM, and 11 CON subjects, all matched for BMI, and aerobic fitness. IHL content was measured using proton magnetic resonance spectroscopy. Because of high IHL content variability in T2DM patients, this group was separated into a high IHL content group (IHL >= 5.0%, T2DM+ NAFL) and a normal IHL content group (IHL <5.0%, T2DM-non-NAFL) for further analysis.IHL content was increased in NAFL and T2DM+ NAFL subjects (P <0.050 versus CON and T2DM-non-NAFL subjects). Adipose tissue insulin sensitivity index (Adipo-IRi) was higher in NAFL (P<0.050 versus CON and T2DM-non-NAFL subjects) and in T2DM+ NAFL subjects (P= 0.055 versus CON subjects, P<0.050 versus T2DM-non-NAFL subjects). Suppression of plasma-free fatty acids (P= 0.046) was lower in NAFL compared with CON subjects, with intermediate values for T2DM-non-NAFL, and T2DM+ NAFL subjects. Suppression of endogenous glucose production (EGP) and insulin-stimulated glucose disposal (Delta R-d) was comparable between NAFL, T2DM-non-NAFL, and T2DM+ NAFL subjects (all P> 0.05), and was lower in comparison with CON subjects (all P<0.01). Metabolic flexibility was lower in T2DM-non-NAFL subjects (P= 0.047) and NAFL subjects (P= 0.059) compared with CON subjects. Adipo-IRi (r= 0.652, P<0.001), hepatic insulin resistance index (HIRi) (r= 0.576, P= 0.001), and Delta R-d (r=-0.653, P<0.001) correlated with IHL content.Individuals with NAFL suffer from metabolic perturbations to a similar degree as T2DM patients. NAFL is an important feature leading to severe insulin resistance and should be viewed as a serious health threat for the development of T2DM.
KW - TISSUE INSULIN-RESISTANCE
KW - INTRAHEPATIC TRIGLYCERIDE CONTENT
KW - MAGNETIC-RESONANCE-SPECTROSCOPY
KW - HEPATIC STEATOSIS
KW - SKELETAL-MUSCLE
KW - GLUCOSE-PRODUCTION
KW - NATURAL-HISTORY
KW - DISEASE
KW - SENSITIVITY
KW - PREVALENCE
U2 - 10.1042/CS20170261
DO - 10.1042/CS20170261
M3 - Article
C2 - 28620012
SN - 0143-5221
VL - 131
SP - 1905
EP - 1917
JO - Clinical Science
JF - Clinical Science
IS - 15
ER -