Relationship between hepatic/visceral fat and hepatic insulin resistance in nondiabetic and type 2 diabetic subjects.
OBJECTIVE
Abdominal fat accumulation (visceral/hepatic) has been associated with hepatic insulin resistance (IR) in obesity and type 2 diabetes (T2DM). We examined the relationship between visceral/hepatic fat accumulation and hepatic IR/accelerated gluconeogenesis (GNG).


METHODS
In 14 normal glucose tolerant (NGT) (body mass index [BMI] = 25 +/- 1 kg/m(2)) and 43 T2DM (24 nonobese, BMI = 26 +/- 1; 19 obese, BMI = 32 +/- 1 kg/m(2)) subjects, we measured endogenous (hepatic) glucose production (3-(3)H-glucose) and GNG ((2)H(2)O) in the basal state and during 240 pmol/m(2)/min euglycemic-hyperinsulinemic clamp, and liver (LF) subcutaneous (SAT)/visceral (VAT) fat content by magnetic resonance spectroscopy/magnetic resonance imaging.


RESULTS
LF was increased in lean T2DM compared with lean NGT (18% +/- 3% vs 9% +/- 2%, P < .03), but was similar in lean T2DM and obese T2DM (18% +/- 3% vs 22% +/- 3%; P = NS). Both VAT and SAT increased progressively from lean NGT to lean T2DM to obese T2DM. T2DM had increased basal endogenous glucose production (EGP) (NGT, 15.1 +/- 0.5; lean T2DM, 16.3 +/- 0.4; obese T2DM, 17.2 +/- 0.6 micromol/min/kg(ffm); P = .02) and basal GNG flux (NGT, 8.6 +/- 0.4; lean T2DM, 9.6 +/- 0.4; obese T2DM, 11.1 +/- 0.6 micromol/min/kg(ffm); P = .02). Basal hepatic IR index (EGP x fasting plasma insulin) was increased in T2DM (NGT, 816 +/- 54; lean T2DM, 1252 +/- 164; obese T2DM, 1810 +/- 210; P = .007). In T2DM, after accounting for age, sex, and BMI, both LF and VAT, but not SAT, were correlated significantly (P < .05) with basal hepatic IR and residual EGP during insulin clamp. Basal percentage of GNG and GNG flux were correlated positively with VAT (P < .05), but not with LF. LF, but not VAT, was correlated with fasting insulin, insulin-stimulated glucose disposal, and impaired FFA suppression by insulin (all P < .05).


CONCLUSIONS
Abdominal adiposity significantly affects both lipid (FFA) and glucose metabolism. Excess VAT primarily increases GNG flux. Both VAT and LF are associated with hepatic IR.
Division of Diabetes, Department of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA. amalia@ifc.cnr.it
Amalia
A
Gastaldelli
Kenneth
K
Cusi
Maura
M
Pettiti
Jean
J
Hardies
Yoshinori
Y
Miyazaki
Rachele
R
Berria
Emma
E
Buzzigoli
Anna Maria
AM
Sironi
Eugenio
E
Cersosimo
Ele
E
Ferrannini
Ralph A
RA
Defronzo
D050153:Abdominal Fat / Q000378:metabolism / Q000503:physiopathology*; D000328:Adult; D000375:Aging; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005943:Gluconeogenesis; D015309:Glucose Clamp Technique; D050261:Glycogenolysis; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*
D001786:Blood Glucose; D007328:Insulin