GH peak response to GHRH-arginine: relationship to insulin resistance and other cardiovascular risk factors in a population of adults aged 50-90

Abstract

Objective: To assess the GH response to GHRH-arginine in apparently healthy adults in relation to cardiovascular risk factors.

Design: Cross-sectional.

Patients: Eighty-six male and female volunteers aged 50-90.

Measurements: GH peak response to GHRH-arginine and cardiovascular risk factors, including obesity, insulin resistance, low levels of high density lipoprotein (HDL) cholesterol, elevated triglycerides, and hypertension. The primary outcome measurement was GH response to GHRH-arginine. The relationship between GH peak responses and cardiovascular risk factors was determined after data collection.

Results: GH peaks were highly variable, ranging from 2.3 to 185 microg/l (14% with GH peaks < 9 microg/l). An increasing number of cardiovascular risk factors were associated with a lower mean GH peak (P < 0.0001). By univariate analysis, fasting glucose, insulin, body mass index (BMI), HDL cholesterol and triglycerides were significantly associated with GH peak (all P < 0.0001). Multiple regression analysis revealed that fasting glucose, fasting insulin, BMI, triglycerides and sex accounted for 54% of GH peak variability. The role of abdominal fat as it relates to GH peak was explored in a subset of 45 subjects. Trunk fat and abdominal subregion fat measured by dual energy X-ray absorptiometry (DXA) were inversely related to GH peak (P < 0.008 and 0.001, respectively). Analysis of this subgroup by multiple regression revealed that subregion abdominal fat became the significant obesity-related determinant of GH peak, but still lagged behind fasting insulin and glucose.

Conclusions: GH response to secretagogues was highly variable in apparently healthy adults aged 50-90 years. Peak GH was significantly related to fasting glucose, insulin, BMI, HDL cholesterol, triglycerides, trunk fat and abdominal subregion fat, with fasting glucose ranking first by multiple regression analysis. There was a strong relationship between cardiovascular risk factors and low GH, with individual risk factors being additive. Although these data do not differentiate between low GH being a cause or an effect of these cardiovascular risk factors, they indicate that the relationship between low GH and increased cardiovascular risk may be physiologically important in the absence of pituitary disease.

Fig. 1

Variability of peak GH responses to GHRH-arginine. Individual peak GH responses in 86 volunteers between 50 and 90 years of age.

Fig. 2

Relationship of GH peak to cardiovascular risk factors. (a) Mean log GH peak was significantly lower in 19 volunteers with three or more cardiovascular risk factors compared to 67 with two or fewer cardiovascular risk factors. (b) GH peak in 86 subjects divided according to number of cardiovascular risk factors [0 (n = 22), 1 (n = 23), 2 (n = 22), 3 (n = 13), and 4 (n = 6)]. Median arithmetic values for GH peak are displayed. Statistics performed by Student's t-test (a) and one-way analysis of variance (anova) (b). (1 ng/ml GH = 1 µg/l.)

Fig. 3

(a) Relationship of body mass index (BMI in kg/m²) to GH peak. Subjects with BMI < 27·5 are represented by filled circles (•) and those with BMI ≥ 27·5 by open squares (□). Separate regression lines were drawn for subjects with BMI < 27·5 (solid line) and those with BMI ≥ 27·5 (dashed line). Relationship between GH and BMI was significant when BMI was < 27·5 (r = –0·516, P < 0·0001) but was lost when only those with BMI ≥ 27·5 were considered (r = –0·181, P < 0·253). (b) Relationship of fasting glucose to GH peak according to BMI. For BMI < 27·5 the relationship between GH and fasting glucose was significant (r = –0·580, P < 0·0001), as was the relationship between GH and glucose in BMI ≥ 27·5 (r = –0·495, P < 0·001). (1 ng/ml GH = 1 µg/l.)