title: Hepatic insulin clearance is closely related to metabolic syndrome components.
abstract: OBJECTIVE
  Insulin clearance is decreased in type 2 diabetes mellitus (T2DM) for unknown reasons. Subjects with metabolic syndrome are hyperinsulinemic and have an increased risk of T2DM. We aimed to investigate the relationship between hepatic insulin clearance (HIC) and different components of metabolic syndrome and tested the hypothesis that HIC may predict the risk of metabolic syndrome.
  
  
  METHODS
  Individuals without diabetes from the Metabolic Syndrome Berlin Brandenburg (MeSyBePo) study (800 subjects with the baseline examination and 189 subjects from the MeSyBePo recall study) underwent an oral glucose tolerance test (OGTT) with assessment of insulin secretion (insulin secretion rate [ISR]) and insulin sensitivity. Two indices of HIC were calculated.
  
  
  RESULTS
  Both HIC indices showed lower values in subjects with metabolic syndrome (P < 0.001) at baseline. HIC indices correlate inversely with waist circumference, diastolic blood pressure, fasting glucose, triglycerides, and OGTT-derived insulin secretion index. During a mean follow-up of 5.1 ± 0.9 years, 47 individuals developed metabolic syndrome and 33 subjects progressed to impaired glucose metabolism. Both indices of HIC showed a trend of an association with increased risk of metabolic syndrome (HICC-peptide odds ratio 1.13 [95% CI 0.97-1.31], P = 0.12, and HICISR 1.38 [0.88-2.17], P = 0.16) and impaired glucose metabolism (HICC-peptide 1.12 [0.92-1.36], P = 0.26, and HICISR 1.31 [0.74-2.33] P = 0.36), although point estimates reached no statistical significance.
  
  
  CONCLUSIONS
  HIC was associated with different components of metabolic syndrome and markers of insulin secretion and insulin sensitivity. Decreased HIC may represent a novel pathophysiological mechanism of the metabolic syndrome, which may be used additionally for early identification of high-risk subjects.
authors.affiliation: Corresponding author: Natalia Rudovich, rudovich@dife.de.
authors.forename: Olga
authors.initials: O
authors.lastname: Pivovarova
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bernigau
authors.forename: Thomas
authors.initials: T
authors.lastname: Bobbert
authors.forename: Frank
authors.initials: F
authors.lastname: Isken
authors.forename: Matthias
authors.initials: M
authors.lastname: Möhlig
authors.forename: Joachim
authors.initials: J
authors.lastname: Spranger
authors.forename: Martin O
authors.initials: MO
authors.lastname: Weickert
authors.forename: Martin
authors.initials: M
authors.lastname: Osterhoff
authors.forename: Andreas F H
authors.initials: AF
authors.lastname: Pfeiffer
authors.forename: Natalia
authors.initials: N
authors.lastname: Rudovich
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D005215:Fasting; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology*; D008875:Middle Aged; D012306:Risk; D014280:Triglycerides / Q000097:blood; D055105:Waist Circumference
chemical_list: D007328:Insulin; D014280:Triglycerides
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