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IGF-1 levels across the spectrum of normal to elevated in acromegaly: relationship to insulin sensitivity, markers of cardiovascular risk and body composition

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Abstract

Purpose

Activity of acromegaly is gauged by levels of GH and IGF-1 and epidemiological studies demonstrate that their normalization reduces acromegaly’s excess mortality rate. However, few data are available linking IGF-1 levels to features of the disease that may relate to cardiovascular (CV) risk. Therefore, we tested the hypothesis that serum IGF-1 levels relative to the upper normal limit relate to insulin sensitivity, serum CV risk markers and body composition in acromegaly.

Methods

In this prospective, cross-sectional study conducted at a pituitary tumor referral center we studied 138 adult acromegaly patients, newly diagnosed and previously treated surgically, with fasting and post-oral glucose levels of endocrine and CV risk markers and body composition assessed by DXA.

Results

Active acromegaly is associated with lower insulin sensitivity, body fat and CRP levels than acromegaly in remission. %ULN IGF-1 strongly predicts insulin sensitivity, better than GH and this persists after adjustment for body fat and lean tissue mass. %ULN IGF-1 also relates inversely to CRP levels and fat mass, positively to lean tissue and skeletal muscle estimated (SME) by DXA, but not to blood pressure, lipids, BMI or waist circumference. Gender interacts with the IGF-1-lean tissue mass relationship.

Conclusions

Active acromegaly presents a unique combination of features associated with CV risk, reduced insulin sensitivity yet lower body fat and lower levels of some serum CV risk markers, a pattern that is reversed in remission. %ULN IGF-1 levels strongly predict these features. Given the known increased CV risk of active acromegaly, these findings suggest that of these factors insulin resistance is most strongly related to disease activity and potentially to the increased CV risk of active acromegaly.

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Acknowledgments

Funded by NIH Grants R01 DK 064720 and K24 DK 073040 to P.U.F., and in part by Columbia University’s CTSA Grant No. UL1 RR 024156 from NCRR/NIH, an Investigator Initiated Grant from Novartis Pharmaceuticals and a gift from Dr. and Mrs. Leo Guthart.

Conflict of interest

P.U.F. has received research Grant support from Novartis Pharmaceuticals. T.J.R, Z.J., W.S., C.M.R-V., JC.F., J.N.B, J.K., K.D.P. have nothing to disclose.

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Authors and Affiliations

  1. Department of Medicine, Columbia University, College of Physicians and Surgeons, 650 West 168th Street, 9-905, New York, NY, 10032, USA

    Tirissa J. Reid, Wei Shen, Carlos M. Reyes-Vidal, Jean Carlos Fernandez & Pamela U. Freda

  2. Department of Biostatistics, Columbia University, College of Physicians and Surgeons, New York, NY, 10032, USA

    Zhezhen Jin

  3. Department of Neurosurgery, Columbia University, College of Physicians and Surgeons, New York, NY, 10032, USA

    Jeffrey N. Bruce

  4. Department of Neurosurgery, Mt. Sinai School of Medicine, New York, NY, USA

    Jane Kostadinov & Kalmon D. Post

  5. Department of Medicine, Mt. Sinai School of Medicine, New York, NY, USA

    Kalmon D. Post

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  1. Tirissa J. Reid
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  2. Zhezhen Jin
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  3. Wei Shen
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  4. Carlos M. Reyes-Vidal
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  5. Jean Carlos Fernandez
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  6. Jeffrey N. Bruce
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  7. Jane Kostadinov
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  8. Kalmon D. Post
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  9. Pamela U. Freda
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Correspondence to Pamela U. Freda.

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Clinical trials #: NCT01809808.

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Reid, T.J., Jin, Z., Shen, W. et al. IGF-1 levels across the spectrum of normal to elevated in acromegaly: relationship to insulin sensitivity, markers of cardiovascular risk and body composition. Pituitary 18, 808–819 (2015). https://doi.org/10.1007/s11102-015-0657-2

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