title: Chronic peripheral hyperinsulinemia in type 1 diabetic patients after successful combined pancreas-kidney transplantation does not affect ectopic lipid accumulation in skeletal muscle and liver.
abstract: OBJECTIVE
  So far it is unclear whether chronic peripheral hyperinsulinemia per se might contribute to ectopic lipid accumulation and consequently insulin resistance. We investigated the effects of systemic instead of portal insulin release in type 1 diabetic patients after successful pancreas-kidney transplantation (PKT) with systemic venous drainage on the intracellular lipid content in liver and soleus muscle, endogenous glucose production (EGP), and insulin sensitivity.
  
  
  METHODS
  In nine PKT patients and nine matching nondiabetic control subjects, intrahepatocellular lipids (IHCLs) and intramyocellular lipids (IMCLs) were measured using (1)H nuclear magnetic resonance spectroscopy. Fasting EGP was measured using d-[6,6-(2)H(2)]glucose tracer dilution. A 3-h 75-g oral glucose tolerance test (OGTT) allowed us to assess kinetics of glucose, free fatty acids, insulin, and C-peptide concentrations in plasma and to calculate the clamp-like index (CLIX) for insulin sensitivity and the hepatic insulin resistance (HIR) index.
  
  
  RESULTS
  The PKT patients displayed approximately twofold increased fasting insulin (20 +/- 6 vs. 9 +/- 3 microU/ml; P < 0.0002) compared with that in nondiabetic control subjects and approximately 10% increased fasting glucose (P < 0.02) concentrations, but during the OGTT areas under the concentration curves of C-peptide and insulin were similar. IHCL (PKT, 2.9 +/- 2.5%; nondiabetic control subjects, 4.4 +/- 6.6%), IMCL (PKT, 1.0 +/- 0.4%; nondiabetic control subjects, 1.0 +/- 0.5%), CLIX (PKT, 8 +/- 2; nondiabetic control subjects, 7 +/- 3), HIR (PKT, 25.6 +/- 13.2; nondiabetic control subjects, 35.6 +/- 20 [mg * min(-1) * kg(-1)] x [microU/ml]), and EGP (PKT, 1.6 +/- 0.2; nondiabetic control subjects, 1.7 +/- 0.2 mg * min(-1) * kg(-1)) were comparable between PKT patients and nondiabetic control subjects. IHCL was negatively correlated with CLIX in all participants (r = -0.55; P < 0.04).
  
  
  CONCLUSIONS
  Despite fasting peripheral hyperinsulinemia because of systemic venous drainage, type 1 diabetic patients after PKT show similar IHCL, IMCL, insulin sensitivity, and fasting EGP in comparison with nondiabetic control subjects. These results suggest that systemic hyperinsulinemia per se does not cause ectopic lipid accumulation in liver and skeletal muscle.
authors.affiliation: Hietzing Hospital, 3rd Medical Department of Metabolic Diseases and Nephrology, Vienna, Austria.
authors.forename: Marietta
authors.initials: M
authors.lastname: Stadler
authors.forename: Christian
authors.initials: C
authors.lastname: Anderwald
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pacini
authors.forename: Stefan
authors.initials: S
authors.lastname: Zbýn
authors.forename: Miriam
authors.initials: M
authors.lastname: Promintzer-Schifferl
authors.forename: Martina
authors.initials: M
authors.lastname: Mandl
authors.forename: Martin
authors.initials: M
authors.lastname: Bischof
authors.forename: Stephan
authors.initials: S
authors.lastname: Gruber
authors.forename: Peter
authors.initials: P
authors.lastname: Nowotny
authors.forename: Anton
authors.initials: A
authors.lastname: Luger
authors.forename: Rudolf
authors.initials: R
authors.lastname: Prager
authors.forename: Michael
authors.initials: M
authors.lastname: Krebs
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001794:Blood Pressure; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D003928:Diabetic Nephropathies / Q000601:surgery; D005215:Fasting; D005260:Female; D005500:Follow-Up Studies; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006946:Hyperinsulinism / Q000453:epidemiology*; D007328:Insulin / Q000097:blood; D016030:Kidney Transplantation / Q000502:physiology*; D008055:Lipids / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000503:physiopathology; D016035:Pancreas Transplantation / Q000502:physiology*; D012016:Reference Values
chemical_list: D007328:Insulin; D008055:Lipids; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005947:Glucose