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Published on: June 3, 2018
Normal IGF-I and enhanced IGFBP-3 response to very low rhGH dose in patients with dilated cardiomyopathy
Insights
Well-nourished patients with dilated cardiomyopathy (DCM) maintain peripheral growth hormone (GH) sensitivity. DCM patients show increased insulin-like growth factor-binding protein 3 (IGFBP-3) response to recombinant human GH (rhGH) stimulation.
Area of Science:
- Endocrinology
- Cardiology
Background:
- Dilated cardiomyopathy (DCM) is associated with potential alterations in growth hormone (GH) and insulin-like growth factor (IGF) axis.
- Previous studies suggest preserved peripheral GH sensitivity in well-nourished DCM patients.
Purpose of the Study:
- To investigate peripheral GH sensitivity in DCM patients using a low-dose recombinant human GH (rhGH) stimulation test.
- To assess the response of IGF-I and IGFBP-3 levels to rhGH in DCM patients compared to healthy controls.
Main Methods:
- 10 DCM patients and 9 age-matched healthy controls received subcutaneous rhGH (2.5 microg/kg/day) for 4 days.
- Fasting serum IGF-I and IGFBP-3 levels were measured at baseline and after rhGH administration.
- Statistical analysis was performed to compare responses between groups.
Main Results:
- Basal IGF-I levels were not significantly lower in DCM patients compared to controls.
- rhGH administration increased IGF-I levels in both DCM patients and controls, with a similar percentage increase in DCM.
- rhGH significantly increased IGFBP-3 levels in DCM patients, but not in controls, indicating enhanced IGFBP-3 sensitivity.
Conclusions:
- Peripheral GH sensitivity is preserved in well-nourished DCM patients, even at the lowest effective rhGH dose.
- DCM patients exhibit enhanced sensitivity of IGFBP-3 to rhGH stimulation.
- These findings contribute to understanding the GH-IGF axis in DCM and potential therapeutic implications.
Abstract:
Well-nourished patients with dilated cardiomyopathy (DCM) show slight reduction of mean basal IGF-I levels which, however, display a response to a rhGH dose as low as 5.0 microg/kg/day similar to that of age-matched control subjects (CS). To further investigate peripheral GH sensitivity, we studied the IGF-I and IGFBP-3 responses to 4-day s.c. 2.5 microg/kg/day rhGH administration, the lowest effective dose able to increase IGF-I levels in normal subjects, in 10 DCM patients [age (mean+/-SE): 57.6+/-1.0 yr, body mass index (BMI): 24.0+/-1.2 kg/m2, left ventricular ejection fraction: 26.2+/-3.2%, NYHA (New York Heart Association): I/0, II/4, III/4, IV/2] and in 9 age-matched healthy CS (age: 55.3+/-1.2 yr, BMI: 23.7+/-1.8 kg/m2). Basal IGF-I levels in DCM were lower though not significantly than those in CS (147.7+/-9.8 vs 174.7+/-17.0 microg/l). Basal IGFBP-3 levels in DCM were similar to those in CS (3.1+/-0.3 vs 2.7+/-0.2 mg/l). In CS 4-day rhGH increased IGF-I levels (222.4+/-14.9 microg/l; p<0.01 vs baseline) but did not modify IGFBP-3 levels (3.0+/-0.2 mg/l). In DCM IGF-I levels were increased by 4-day rhGH administration (175.7+/-11.0 microg/l; p<0.05 vs baseline) with a similar percent extent than in CS. On the other hand, in DCM, but not in CS, 4-day rhGH significantly increased IGFBP-3 levels (3.5+/-0.3 mg/l; p<0.05 vs baseline). Therefore, in conclusion, testing with the lowest effective rhGH dose further suggest that peripheral GH sensitivity in well-nourished DCM is preserved. On the other hand, DCM patients show enhanced IGFBP-3 sensitivity to stimulation by rhGH.
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