Fatty liver in type 2 diabetes mellitus: relation to regional adiposity, fatty acids, and insulin resistance

Abstract

. 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.

Relationship between the Serum Concentrations of C-reactive Protein and Parameters of Adiposity and Insulin Resistance in Patients with Type 2 Diabetes Mellitus

“…Among the non-diabetic subjects, serum CRP was significantly correlated with the VFA in subjects with BMI≥25, but not in those with BMI<25; there was no significant correlation between serum CRP with L/S ratio or SFA in the non-diabetic subjects, irrespective of BMI. Thus, serum CRP showed no significant correlation with VFA and SFA in the nonobese subjects (BMI<25) ( Table 3), consistent with previous reports [7,17].…”

Reduced intrahepatic fat content is associated with increased whole-body lipid oxidation in patients with type 1 diabetes

“…In agreement with the hypothesis that ectopic fat accumulation may be related to impaired insulin action, an increased IMCL content in association with peripheral insulin resistance was reported in patients with type 1 diabetes as well as in patients with type 2 diabetes and their relatives [4]. More recently it was suggested that ectopic fat accumulation within the liver may be also associated with peripheral and hepatic insulin resistance in nondiabetic individuals [5,6] and is common in obese patients with type 2 diabetes [20]. Some authors suggest that fatty liver represents a body composition manifestation of obesity and visceral adiposity in insulin-resistant subjects [21], but at the same time they suggest that the impact on insulin sensitivity is determined regardless of intra-abdominal and overall adiposity [6].…”

Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease: sites and mechanisms

“…Since hepatic insulin resistance was significantly related to liver fat content independently of BMI, subcutaneous fat volume and intra-abdominal fat volume (as assessed by MRI), the authors concluded that hepatic steatosis rather than adipose tissue triglyceride content can be a major determinant of insulin resistance in humans. Kelly et al [46] recently reported that the presence of liver steatosis (assessed using computerised tomography criteria) in patients with type 2 diabetes is associated with more severe insulin resistance (during a 6 pmol min −1 kg −1 insulin clamp). Using both a low-dose (1.5 pmol min −1 kg −1 ) and a high-dose (6 pmol min −1 kg −1 ) insulin infusion, we have conclusively demonstrated the co-existence of hepatic and peripheral insulin resistance in biopsy-proven NAFLD independent of obesity and diabetes.…”