. Fatty liver in type 2 diabetes mellitus: relation to regional adiposity, fatty acids, and insulin resistance. Am J Physiol Endocrinol Metab 285: E906-E916, 2003; 10.1152/ajpendo.00117.2003.-The current study was undertaken to examine metabolic and body composition correlates of fatty liver in type 2 diabetes mellitus (DM). Eighty-three men and women with type 2 DM [mean body mass index (BMI): 34 Ϯ 0.5 kg/m 2 ] and without clinical or laboratory evidence of liver dysfunction had body composition assessments of fat mass (FM), visceral adipose tissue (VAT), liver and spleen computed tomography (CT) attenuation (ratio of liver to spleen), muscle CT attenuation, and thigh adiposity; these assessments were also performed in 12 lean and 15 obese nondiabetic volunteers. Insulin sensitivity was measured with a euglycemic insulin infusion (40 mU ⅐ m Ϫ2 ⅐ min Ϫ1 ) combined with systemic indirect calorimetry to assess glucose and lipid oxidation, and with infusions of [ 2 H2]glucose for assessment of endogenous glucose production. A majority of those with type 2 DM (63%) met CT criteria for fatty liver, compared with 20% of obese and none of the lean nondiabetic volunteers. Fatty liver was most strongly correlated with VAT (r ϭ Ϫ0.57, P Ͻ 0.0001) and less strongly but significantly associated with BMI (r ϭ Ϫ0.42, P Ͻ 0.001) and FM (r ϭ Ϫ0.37, P Ͻ 0.001), but only weakly associated with subcutaneous adiposity (r ϭ Ϫ0.29; P Ͻ 0.01). Fatty liver was also correlated with subfascial adiposity of skeletal muscle (r ϭ Ϫ0.44; P Ͻ 0.01). Volunteers with type 2 DM and fatty liver were substantially more insulin resistant those with type 2 DM but without fatty liver (P Ͻ 0.001) and had higher levels of plasma free fatty acids (P Ͻ 0.01) and more severe dyslipidemia (P Ͻ 0.01), a pattern observed in both genders. Plasma levels of cytokines were increased in relation to fatty liver (r ϭ Ϫ0.34; P Ͻ 0.01). In summary, fatty liver is relatively common in overweight and obese volunteers with type 2 DM and is an aspect of body composition related to severity of insulin resistance, dyslipidemia, and inflammatory markers.

OBJECTIVE -Moderate weight loss is recommended for overweight and obese patients with type 2 diabetes, and conjunctive use of weight loss medication has been advocated. The current study examined weight loss-dependent and -independent effects of the intestinal lipase inhibitor orlistat at 6 months of treatment, using behavioral intervention (Int) combined with randomized, double-blinded, placebo (P)-controlled treatment with orlistat (O). RESEARCH DESIGN AND METHODS -Metabolic control, insulin sensitivity (IS), regional fat distribution, and fat content in liver and muscle were measured in 39 volunteers with type 2 diabetes in whom all antidiabetic medication was withdrawn 1 month preceding randomization. Weight loss was equivalent in the IntϩO and IntϩP groups, respectively (Ϫ10.3 Ϯ 1.3 vs. Ϫ8.9 Ϯ 1.1%), and there were identical decreases in visceral adipose tissue (VAT), fat mass (FM), thigh adiposity, and hepatic steatosis. CONCLUSIONS -At equivalent weight loss, conjunctive use of orlistat resulted in greater improvement in FFA levels and IS. RESULTS -Weight loss resulted in substantial improvement

MRI can be used to quantify lipid within human muscle tissue. MRI can also be used to detect differences in muscle lipid content among various muscle groups and between normal-weight and obese subjects.

Skeletal muscle insulin resistance (IR) is typically severe in type 2 diabetes mellitus (DM). However, the factors that account for interindividual differences in the severity of IR are not well understood. The current study was undertaken to examine the respective roles of plasma FFA, regional adiposity, and other metabolic factors as determinants of the severity of skeletal muscle IR in type 2 DM. Twenty-three subjects (12 women and 11 men) with type 2 DM underwent positron emission tomography imaging using [18F]2-fluoro-2-deoxyglucose during euglycemic insulin infusions (120 mU/min x m2) to measure skeletal muscle IR, using Patlak analysis of the tissue activity curves. Body composition analysis included body mass index, fat mass, and fat-free mass by dual energy x-ray tomography, and computed tomography determinations of visceral adiposity, thigh adipose tissue distribution, and muscle composition. Body mass index, fat mass, subfascial adiposity in the thigh, and visceral adipose tissue (VAT) were all significantly related to skeletal muscle IR (r = -0.48 to -0.63; P < 0.01). However, the strongest simple correlate of IR in skeletal muscle was insulin-suppressed plasma FFA (r = -0.81; P < 0.001). VAT was the sole component of adiposity that significantly correlated with insulin-suppressed plasma FFA concentration (r = 0.64; P < 0.001). These findings indicate that the severity of skeletal muscle IR in type 2 DM is closely related to the IR of suppressing lipolysis and that plasma fatty acids and VAT are key elements mediating the link between obesity and skeletal muscle IR in type 2 DM.

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