title: Studies of insulin resistance in patients with clinical and subclinical hypothyroidism.
abstract: OBJECTIVE
  Although clinical hypothyroidism (HO) is associated with insulin resistance, there is no information on insulin action in subclinical hypothyroidism (SHO).
  
  
  METHODS
  To investigate this, we assessed the sensitivity of glucose metabolism to insulin both in vivo (by an oral glucose tolerance test) and in vitro (by measuring insulin-stimulated rates of glucose transport in isolated monocytes with flow cytometry) in 21 euthyroid subjects (EU), 12 patients with HO, and 13 patients with SHO.
  
  
  RESULTS
  All three groups had comparable plasma glucose levels, with the HO and SHO having higher plasma insulin than the EU (P<0.05). Homeostasis model assessment index was increased in HO (1.97+/-0.22) and SHO (1.99+/-0.13) versus EU (1.27+/-0.16, P<0.05), while Matsuda index was decreased in HO (3.89+/-0.36) and SHO (4.26+/-0.48) versus EU (7.76+/-0.87, P<0.001), suggesting insulin resistance in both fasting and post-glucose state. At 100 microU/ml insulin: i) GLUT4 levels on the monocyte plasma membrane were decreased in both HO (215+/-19 mean fluorescence intensity, MFI) and SHO (218+/-24 MFI) versus EU (270+/-25 MFI, P=0.03 and 0.04 respectively), and ii) glucose transport rates in monocytes from HO (481+/-30 MFI) and SHO (462+/-19 MFI) were decreased versus EU (571+/-15 MFI, P=0.04 and 0.004 respectively).
  
  
  CONCLUSIONS
  In patients with HO and SHO: i) insulin resistance was comparable; ii) insulin-stimulated rates of glucose transport in isolated monocytes were decreased due to impaired translocation of GLUT4 glucose transporters on the plasma membrane; iii) these findings could justify the increased risk for insulin resistance-associated disorders, such as cardiovascular disease, observed in patients with HO or SHO.
authors.affiliation: Hellenic National Center for Research, Prevention and Treatment of Diabetes Mellitus and its Complications (HNDC), GR-10675 Athens, Greece.
authors.forename: Eirini
authors.initials: E
authors.lastname: Maratou
authors.forename: Dimitrios J
authors.initials: DJ
authors.lastname: Hadjidakis
authors.forename: Anastasios
authors.initials: A
authors.lastname: Kollias
authors.forename: Katerina
authors.initials: K
authors.lastname: Tsegka
authors.forename: Melpomeni
authors.initials: M
authors.lastname: Peppa
authors.forename: Maria
authors.initials: M
authors.lastname: Alevizaki
authors.forename: P
authors.initials: P
authors.lastname: Mitrou
authors.forename: V
authors.initials: V
authors.lastname: Lambadiari
authors.forename: Eleni
authors.initials: E
authors.lastname: Boutati
authors.forename: Daniel
authors.initials: D
authors.lastname: Nikzas
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Tountas
authors.forename: Theofanis
authors.initials: T
authors.lastname: Economopoulos
authors.forename: Sotirios A
authors.initials: SA
authors.lastname: Raptis
authors.forename: George
authors.initials: G
authors.lastname: Dimitriadis
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D005215:Fasting / Q000097:blood; D005951:Glucose Tolerance Test; D051274:Glucose Transporter Type 3 / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006801:Humans; D007037:Hypothyroidism / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D013960:Thyroid Function Tests
chemical_list: D001786:Blood Glucose; D051274:Glucose Transporter Type 3; D051275:Glucose Transporter Type 4; D007328:Insulin; C495687:SLC2A3 protein, human; C495692:SLC2A4 protein, human