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The Insulin-Like Growth Factor Axis and Plasma Lipid Levels in the Elderly¹

Cattedra di Geriatria (G.P.C., A.M., N.V., V.F., M.M., G.V.) e Cattedra di Scienza dell’Alimentazione (E.D.), Università di Parma, Parma, Italy; Diagnostic Systems Laboratories, Inc. (P.D.K.L.), Webster, Texas 77598; the Departments of Pediatrics (R.L.H.) and Medicine (A.R.H.), Stanford University, Stanford, California 94305; and Geriatric Research, Education, and Clinical Center, Veterans Administration Palo Alto Health Care System (A.R.H.), Palo Alto, California 94304

Address all correspondence and requests for reprints to: Dr. Gian Paolo Ceda, Cattedra di Geriatria, Università di Parma, Ospedale G. Stuard, Via Don Bosco 2, 43100 Parma, Italy.

The activity of the hypothalamic-GH-insulin-like growth factor (IGF) network declines with age. It has recently been shown that increased cardiovascular mortality occurs in adults with GH deficiency. As hypercholesterolemia is common in GH-deficient adults, and because there is experimental evidence that GH may play a role in regulating plasma cholesterol, we decided to investigate the activity of the GH-IGF axis in an elderly population by measuring serum IGF-I, IGF-II, and IGF-binding protein-3 (IGFBP-3) levels and to study their relationship with blood lipid levels. One hundred and thirty-two elderly subjects, 52 men and 80 women, were studied (age range, 60–91 yr). Men had significantly lower levels of IGFBP-3, high density lipoprotein cholesterol (HDL-C) and apoprotein A1 (ApoA1) compared to the women, whereas IGF-I and IGF-II were only slightly lower. Using linear regression analysis, we observed an inverse relationship of age with IGF-I (r = -0.35; P < 0.001), IGF-II (r = 0.40; P < 0.001), IGFBP-3 (r = 0.52; P < 0.001), body mass index, and lipid levels. Univariate regression analysis showed a strong and positive correlation of both IGF-I and IGFBP-3 with HDL-C and ApoA1. Partial correlation analysis, after adjustment for age and body mass index, showed that IGFBP-3 and IGF-II were still significantly and positively related to HDL-C and ApoA1. Furthermore, a strong association was documented among IGF-I, IGF-II, and IGFBP-3. These data demonstrate that even in an elderly population, further aging is accompanied by a progressive decline in circulating IGF-I, IGF-II, and IGFBP-3, suggesting a continuing diminution of the GH-IGF axis throughout aging. Moreover, the strong correlation between HDL-C and an index of GH secretion, such as IGFBP-3, suggests that GH might play an important role in lipid metabolism in healthy elderly subjects.

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