Association of elevated insulin-like growth factor binding protein-1 with insulin resistance in hyperthyroidism.
OBJECTIVE
Insulin-like growth factor binding-protein-1 (IGFBP-1) has a role in glucose homeostasis and is present at high concentrations in hyperthyroidism. We have investigated the relationship between IGFBP-1 concentration and glucose homeostasis in hyperthyroidism.


METHODS
Patients and controls had intravenous glucose tolerance tests (IVGTT) and/or oral glucose tolerance tests (OGTT). Patients were tested when hyperthyroid and when euthyroid whilst the controls were tested once. The IVGTT was used to assess insulin sensitivity and the OGTT to establish that the study group had abnormal glucose tolerance. The hyperthyroid patients were treated with methimazole to restore euthyroidism.


METHODS
Ten patients (9 females) and 13 healthy controls (9 females) consented to the study. Ten patients and nine controls (7 females) had IVGTT. Six patients (5 females) and six controls (4 females) had OGTT.


METHODS
Glucose, insulin, glucagon, GH and IGFBP-1 were measured during GTT. IGF-I, free thyroid hormones, and TSH concentrations were measured basally.


RESULTS
Hyperthyroid subjects were insulin resistant and 67% had impaired glucose tolerance. Fasting IGFBP-1 levels were doubled in hyperthyroid subjects compared to healthy controls and correlated positively with free T4 (r = 0.84, P < 0.0001), with peak glucose during the OGTT (r = 0.68, P < 0.005) with peak insulin during the IVGTT (r = 0.51, P < 0.005) and negatively with glucose disappearance constant (r = - 0.52, P < 0.005). IGFBP-1 was highly phosphorylated in hyperthyroid and control subjects. Fasting insulin and IGFBP-1 levels were unrelated but IGFBP-1 suppressed acutely during GTT in all groups. GH levels fell less in patients with hyperthyroidism than in normals during GTTs.


CONCLUSIONS
We conclude that in hyperthyroidism thyroid hormones directly increase fasting IGFBP-1 concentration but acute regulation of IGFBP-1 by insulin is normal and that elevated fasting phosphorylated IGFBP-1 concentration is associated with insulin resistance.
Jenkins
R C
RC
Section of Medicine, University Division of Clinical Sciences, Northern General Hospital, Sheffield, UK; Servizio di Endocrinologia, Arcispedale S. Maria Nuova, Reggio Emilia, Italy.
Valcavi
R
R
Zini
M
M
Frasoldati
A
A
Heller
S R
SR
Camacho-Hubner
C
C
Gibson
J M
JM
Westwood
M
M
Ross
R J
RJ
D000328:Adult; D013956:Antithyroid Agents / Q000627:therapeutic use; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005951:Glucose Tolerance Test; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006980:Hyperthyroidism / Q000188:drug therapy / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008713:Methimazole / Q000627:therapeutic use; D013974:Thyroxine / Q000097:blood
D013956:Antithyroid Agents; D001786:Blood Glucose; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D019382:Human Growth Hormone; D008713:Methimazole; D007334:Insulin-Like Growth Factor I; D013974:Thyroxine