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Insulin Action in Adipose Tissue and Muscle in Hypothyroidism

2nd Department of Internal Medicine (G.D., P.M., V.L., E.B., S.A.R.), Research Institute and Diabetes Center, Athens University Medical School, "Attikon" University Hospital, GR-12462 Haidari, Greece; Hellenic National Diabetes Center (E.M., S.A.R.), GR-10675 Athens, Greece; Department of Statistics (D.B.P.), Harokopio University, GR-17671 Athens, Greece; Department of Endocrinology, "Elena Venizelou" Hospital (E.K.), GR-11521 Athens, Greece; and "Evangelismos" Hospital (M.T., N.T.), GR-10676 Athens, Greece

Address all correspondence and requests for reprints to: George Dimitriadis, M.D., D.Phil., 2nd Department of Internal Medicine, Research Institute and Diabetes Center, Athens University, "Attikon" University Hospital, 1 Rimini Street, GR-12462 Haidari, Greece. E-mail: gdimi{at}ath.forthnet.gr and gdimitr{at}med.uoa.gr.

Background: Although insulin resistance in thyroid hormone excess is well documented, information on insulin action in hypothyroidism is limited.

Methods: To investigate this, a meal was given to 11 hypothyroid (HO; aged 45 ± 3 yr) and 10 euthyroid subjects (EU; aged 42 ± 4 yr). Blood was withdrawn for 360 min from veins (V) draining the anterior abdominal sc adipose tissue and the forearm and from the radial artery (A). Blood flow (BF) in adipose tissue was measured with ¹³³Xe and in forearm with strain-gauge plethysmography. Tissue glucose uptake was calculated as (A-V)_glucose(BF), lipoprotein lipase as (A-V)_{Triglycerides}(BF), and lipolysis as [(V-A)_glycerol(BF)]-lipoprotein lipase.

Results: The HO group had higher glucose and insulin levels than the EU group (P < 0.05). In HO vs. EU after meal ingestion (area under curve 0–360 min): 1) BF (1290 ± 79 vs. 1579 ± 106 ml per 100 ml tissue in forearm and 706 ± 105 vs. 1340 ± 144 ml per 100 ml tissue in adipose tissue) and glucose uptake (464 ± 74 vs. 850 ± 155 µmol per 100 ml tissue in forearm and 208 ± 42 vs. 406 ± 47 µmol per 100 ml tissue in adipose tissue) were decreased (P < 0.05), but fractional glucose uptake was similar (28 ± 6 vs. 33 ± 6% per minute in forearm and 17 ± 4 vs. 14 ± 3% per minute in adipose tissue); 2) suppression of lipolysis by insulin was similar; and 3) plasma triglycerides were elevated (489 ± 91 vs. 264 ± 36 nmol/liter·min, P < 0.05), whereas adipose tissue lipoprotein lipase (42 ± 11 vs. 80 ± 21 µmol per 100 ml tissue) and triglyceride clearance (45 ± 10 vs. 109 ± 21 ml per 100 ml tissue) were decreased in HO (P < 0.05).

Conclusions: In hypothyroidism: 1) glucose uptake in muscle and adipose tissue is resistant to insulin; 2) suppression of lipolysis by insulin is not impaired; and 3) hypertriglyceridemia is due to decreased clearance by the adipose tissue.

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