title: Liver fat content and hepatic insulin sensitivity in overweight patients with type 1 diabetes.
abstract: OBJECTIVE
  Patients with type 1 diabetes mellitus (T1DM) lack the portal/peripheral insulin gradient, which might diminish insulin stimulation of hepatic lipogenesis and protect against development of nonalcoholic fatty liver disease (NAFLD). We compared liver fat content and insulin sensitivity of hepatic glucose production and lipolysis between overweight T1DM patients and nondiabetic subjects.
  
  
  METHODS
  We compared 32 overweight adult T1DM patients and 32 nondiabetic subjects matched for age, body mass index (BMI), and gender. Liver fat content was measured using proton magnetic resonance spectroscopy ((1)H-MRS), body composition by magnetic resonance imaging, and insulin sensitivity using the euglycemic-hyperinsulinemic clamp technique (insulin 0.4 mU/kg · min combined with infusion of D-[3-(3)H]glucose). We also hypothesized that low liver fat might protect from obesity-associated increases in insulin requirements and, therefore, determined insulin requirements across BMI categories in 3164 T1DM patients.
  
  
  RESULTS
  Liver fat content was significantly lower in T1DM patients than in nondiabetic subjects (0.6% [25th-75th quartiles, 0.3%-1.1%] vs 9.0% [3.0%-18.0%]; P < .001). The endogenous rate of glucose production (R(a)) during euglycemic hyperinsulinemia was significantly lower (0.4 [-0.7 to 0.8] mg/kg fat-free mass · min vs 0.9 [0.2-1.6] fat-free mass · min; P = .012) and the percent suppression of endogenous Ra by insulin was significantly greater (89% [78%-112%] vs 77% [50%-94%]; p = .009) in T1DM patients than in nondiabetic subjects. Serum nonesterified fatty acid concentrations during euglycemic hyperinsulinemia were significantly lower (78.5 [33.0-155.0] vs 306 [200.0-438.0] μmol/L; P < .001) and the percent suppression of nonesterified fatty acids significantly higher (89.1% [78.6%-93.3%] vs 51.4% [36.5%-71.1%]; P < .001) in T1DM patients than in nondiabetic subjects. Insulin doses were similar across BMI categories.
  
  
  CONCLUSIONS
  T1DM patients might be protected from steatosis and hepatic insulin resistance. Obesity may not increase insulin requirements in T1DM.
authors.affiliation: Minerva Foundation Institute for Medical Research (G.L., K.S., H.Y.-J.), FI-00290 Helsinki, Finland; Department of Medicine (K.S., S.S., H.Y.-J.), University of Helsinki, and Helsinki University Central Hospital, FI-00290 Helsinki, Finland; Helsinki Medical Imaging Center (A.H., N.L.), Helsinki University Central Hospital, FI-00290 Helsinki, Finland; Department of Clinical Sciences (M.O.-M.), Diabetes and Endocrinology, University Hospital Malmö, Lund University, SE-205 02 Malmö, Sweden; Folkhälsan Research Centre (P.-H.G., C.F.), Folkhälsan Institute of Genetics, Biomedicum Helsinki, FI-00290 Helsinki, Finland; and Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (G.L.), Endocrinology Unit, Joan XXIII University Hospital, IISPV Pere Virgili Health Research Institute, Rovira i Virgili University, 43005 Tarragona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Llauradó
authors.forename: Ksenia
authors.initials: K
authors.lastname: Sevastianova
authors.forename: Sanja
authors.initials: S
authors.lastname: Sädevirta
authors.forename: Antti
authors.initials: A
authors.lastname: Hakkarainen
authors.forename: Nina
authors.initials: N
authors.lastname: Lundbom
authors.forename: Marju
authors.initials: M
authors.lastname: Orho-Melander
authors.forename: Per-Henrik
authors.initials: PH
authors.lastname: Groop
authors.forename: Carol
authors.initials: C
authors.lastname: Forsblom
authors.forename: Hannele
authors.initials: H
authors.lastname: Yki-Järvinen
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000378:metabolism*; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D050356:Lipid Metabolism / Q000502:physiology; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D050177:Overweight / Q000150:complications / Q000378:metabolism*
chemical_list: D001786:Blood Glucose