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Relationship between hepatic/visceral fat and hepatic insulin resistance in nondiabetic and type 2 diabetic subjects.

Abstract

BACKGROUND AND AIMS

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.

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  • Authors+Show Affiliations

    ,

    Division of Diabetes, Department of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA. amalia@ifc.cnr.it

    , , , , , , , , ,

    Source

    Gastroenterology 133:2 2007 Aug pg 496-506

    MeSH

    Abdominal Fat
    Adult
    Aging
    Blood Glucose
    Body Mass Index
    Diabetes Mellitus, Type 2
    Female
    Gluconeogenesis
    Glucose Clamp Technique
    Glycogenolysis
    Humans
    Insulin
    Insulin Resistance
    Lipid Metabolism
    Liver
    Magnetic Resonance Imaging
    Magnetic Resonance Spectroscopy
    Male
    Middle Aged
    Obesity

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, Non-P.H.S.

    Language

    eng

    PubMed ID

    17681171

    Citation

    Gastaldelli, Amalia, et al. "Relationship Between Hepatic/visceral Fat and Hepatic Insulin Resistance in Nondiabetic and Type 2 Diabetic Subjects." Gastroenterology, vol. 133, no. 2, 2007, pp. 496-506.
    Gastaldelli A, Cusi K, Pettiti M, et al. Relationship between hepatic/visceral fat and hepatic insulin resistance in nondiabetic and type 2 diabetic subjects. Gastroenterology. 2007;133(2):496-506.
    Gastaldelli, A., Cusi, K., Pettiti, M., Hardies, J., Miyazaki, Y., Berria, R., ... Defronzo, R. A. (2007). Relationship between hepatic/visceral fat and hepatic insulin resistance in nondiabetic and type 2 diabetic subjects. Gastroenterology, 133(2), pp. 496-506.
    Gastaldelli A, et al. Relationship Between Hepatic/visceral Fat and Hepatic Insulin Resistance in Nondiabetic and Type 2 Diabetic Subjects. Gastroenterology. 2007;133(2):496-506. PubMed PMID: 17681171.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Relationship between hepatic/visceral fat and hepatic insulin resistance in nondiabetic and type 2 diabetic subjects. AU - Gastaldelli,Amalia, AU - Cusi,Kenneth, AU - Pettiti,Maura, AU - Hardies,Jean, AU - Miyazaki,Yoshinori, AU - Berria,Rachele, AU - Buzzigoli,Emma, AU - Sironi,Anna Maria, AU - Cersosimo,Eugenio, AU - Ferrannini,Ele, AU - Defronzo,Ralph A, Y1 - 2007/05/01/ PY - 2006/08/07/received PY - 2007/04/19/accepted PY - 2007/8/8/pubmed PY - 2007/9/7/medline PY - 2007/8/8/entrez SP - 496 EP - 506 JF - Gastroenterology JO - Gastroenterology VL - 133 IS - 2 N2 - BACKGROUND AND AIMS: 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. SN - 0016-5085 UR - https://www.unboundmedicine.com/medline/citation/17681171/Relationship_between_hepatic/visceral_fat_and_hepatic_insulin_resistance_in_nondiabetic_and_type_2_diabetic_subjects_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0016-5085(07)00925-0 DB - PRIME DP - Unbound Medicine ER -