• J. Clin. Endocrinol. Metab. · Feb 2011

    Small intestinal alterations in severely obese hyperglycemic subjects.

    • Froukje J Verdam, Jan Willem M Greve, Sedigheh Roosta, Hans van Eijk, Nicole Bouvy, Wim A Buurman, and Sander S Rensen.
    • Department of General Surgery, School for Nutrition, Toxicology, and Metabolism Research Institute Maastricht, Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands.
    • J. Clin. Endocrinol. Metab. 2011 Feb 1;96(2):E379-83.

    ContextType 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.ObjectiveThe objective of the study was to investigate the relation between plasma markers of small intestinal function and chronic hyperglycemia in man.Design, Setting, And ParticipantsWe 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.Main Outcome MeasuresWe 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.ResultsPlasma 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).ConclusionChronically 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.

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