title: Small intestinal alterations in severely obese hyperglycemic subjects.
abstract: BACKGROUND
  Type 2 diabetes mellitus (DM2) is associated with small intestinal hyperplasia and hypertrophy in rodents. Moreover, the small intestine is increasingly acknowledged to play a role in the pathophysiology of DM2.
  
  
  OBJECTIVE
  The objective of the study was to investigate the relation between plasma markers of small intestinal function and chronic hyperglycemia in man.
  
  
  METHODS
  We conducted a cross-sectional observational study of 40 severely obese subjects with chronic hyperglycemia and 30 severely obese subjects without chronic hyperglycemia who were indicated for bariatric surgery.
  
  
  METHODS
  We assessed plasma levels of citrulline, representing small intestinal enterocyte mass, intestinal fatty acid binding protein (I-FABP), a marker of enterocyte loss, and glucagon-like peptide-2, an intestinotrophic factor, and related them to glycated hemoglobin (HbA(1c)) levels.
  
  
  RESULTS
  Plasma citrulline and I-FABP levels were both significantly elevated in subjects with chronic hyperglycemia (HbA(1c) > 6.0%) compared with subjects with a normal HbA(1c) (≤ 6.0%) (citrulline, 35 ± 2.1 μm vs. 26 ± 1.4 μm, P = 0.001; I-FABP, 140 ± 22 pg/ml vs. 69 ± 14 pg/ml, P = 0.001). Moreover, plasma citrulline and I-FABP levels correlated with HbA(1c) levels (citrulline, r(s) = 0.30, P = 0.02; I-FABP, r(s) = 0.33, P = 0.005). The I-FABP to citrulline ratio was higher in subjects with an elevated HbA(1c) (4.0 vs. 3.1, P = 0.03). Plasma glucagon-like peptide-2 levels were not related to citrulline or I-FABP levels (r(s) = 0.06, P = 0.67; r(s) 0.08, P = 0.54, respectively).
  
  
  CONCLUSIONS
  Chronically elevated glucose levels in obese individuals are associated with increased small intestinal enterocyte mass and increased enterocyte loss. These findings argue for the further exploration of the role of the intestine in the pathophysiology of DM2.
authors.affiliation: Department of General Surgery, School for Nutrition, Toxicology, and Metabolism Research Institute Maastricht, Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands.
authors.forename: Froukje J
authors.initials: FJ
authors.lastname: Verdam
authors.forename: Jan Willem M
authors.initials: JW
authors.lastname: Greve
authors.forename: Sedigheh
authors.initials: S
authors.lastname: Roosta
authors.forename: Hans
authors.initials: H
authors.lastname: van Eijk
authors.forename: Nicole
authors.initials: N
authors.lastname: Bouvy
authors.forename: Wim A
authors.initials: WA
authors.lastname: Buurman
authors.forename: Sander S
authors.initials: SS
authors.lastname: Rensen
mesh_terms: D000328:Adult; D001706:Biopsy; D049109:Cell Proliferation; D002908:Chronic Disease; D002956:Citrulline / Q000097:blood; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology; D020895:Enterocytes / Q000502:physiology; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D005260:Female; D053767:Glucagon-Like Peptide 2 / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000473:pathology*; D007421:Intestine, Small / Q000473:pathology*; D008297:Male; D009765:Obesity / Q000473:pathology*; D009929:Organ Size / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002956:Citrulline; D050556:Fatty Acid-Binding Proteins; D053767:Glucagon-Like Peptide 2; D006442:Glycated Hemoglobin; C493320:Fabp1 protein, mouse