Association of elevated insulin-like growth factor binding protein-1 with insulin resistance in hyperthyroidism

Richard C. Jenkins, Roberto Valcavi, Michele Zini, Andrea Frasoldati, Simon R. Heller, Cecilia Camacho-Hubner, J. Martin Gibson, Melissa Westwood, Richard J M Ross

Research output: Contribution to journalArticle

Abstract

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. DESIGN: 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. PATIENTS: 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. MEASUREMENTS: 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.

Original languageEnglish
Pages (from-to)187-195
Number of pages9
JournalClinical Endocrinology
Volume52
Issue number2
DOIs
Publication statusPublished - 2000

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Insulin-Like Growth Factor Binding Protein 1
Hyperthyroidism
Insulin Resistance
Glucose Tolerance Test
Glucose
Insulin
Fasting
Thyroid Hormones
Homeostasis
Methimazole
Glucose Intolerance
Glucagon
Insulin-Like Growth Factor I

ASJC Scopus subject areas

  • Endocrinology

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Association of elevated insulin-like growth factor binding protein-1 with insulin resistance in hyperthyroidism. / Jenkins, Richard C.; Valcavi, Roberto; Zini, Michele; Frasoldati, Andrea; Heller, Simon R.; Camacho-Hubner, Cecilia; Gibson, J. Martin; Westwood, Melissa; Ross, Richard J M.

In: Clinical Endocrinology, Vol. 52, No. 2, 2000, p. 187-195.

Research output: Contribution to journalArticle

Jenkins, RC, Valcavi, R, Zini, M, Frasoldati, A, Heller, SR, Camacho-Hubner, C, Gibson, JM, Westwood, M & Ross, RJM 2000, 'Association of elevated insulin-like growth factor binding protein-1 with insulin resistance in hyperthyroidism', Clinical Endocrinology, vol. 52, no. 2, pp. 187-195. https://doi.org/10.1046/j.1365-2265.2000.00924.x
Jenkins, Richard C. ; Valcavi, Roberto ; Zini, Michele ; Frasoldati, Andrea ; Heller, Simon R. ; Camacho-Hubner, Cecilia ; Gibson, J. Martin ; Westwood, Melissa ; Ross, Richard J M. / Association of elevated insulin-like growth factor binding protein-1 with insulin resistance in hyperthyroidism. In: Clinical Endocrinology. 2000 ; Vol. 52, No. 2. pp. 187-195.
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AU - Jenkins, Richard C.

AU - Valcavi, Roberto

AU - Zini, Michele

AU - Frasoldati, Andrea

AU - Heller, Simon R.

AU - Camacho-Hubner, Cecilia

AU - Gibson, J. Martin

AU - Westwood, Melissa

AU - Ross, Richard J M

PY - 2000

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N2 - 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. DESIGN: 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. PATIENTS: 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. MEASUREMENTS: 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.

AB - 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. DESIGN: 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. PATIENTS: 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. MEASUREMENTS: 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.

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