Reduced growth hormone secretion in obesity is associated with smaller LDL and HDL particle size.

OBJECTIVE: Reduced growth hormone (GH) secretion is observed in obesity and may contribute to increases in cardiovascular disease (CVD) risk. Lipoprotein characteristics including increased small dense low-density lipoprotein (LDL) particles are known independent risk factors for CVD. We hypothesized that reduced GH secretion in obesity would be associated with a more atherogenic lipid profile including increased small dense LDL particles. DESIGN: To evaluate this hypothesis, we studied 102 normal weight and obese men and women using standard GH stimulation testing to assess GH secretory capacity and performed comprehensive lipoprotein analyses including determination of lipoprotein particle size and subclass concentrations using proton NMR spectroscopy. RESULTS: Obese subjects were stratified into reduced or sufficient GH secretion based on the median peak-stimulated GH (≤6·25 µg/l). Obese subjects with reduced GH secretion (n = 35) demonstrated a smaller mean LDL and HDL particle size in comparison to normal weight subjects (n = 33) or obese subjects with sufficient GH (n = 34) by ANOVA (P < 0·0001). Univariate analyses demonstrated peak-stimulated GH was positively associated with LDL (r = 0·50; P < 0·0001) and HDL (r = 0·57; P < 0·0001), but not VLDL (P = 0·06) particle size. Multivariate regression analysis controlling for age, gender, race, ethnicity, tobacco, use of lipid-lowering medication, BMI and HOMA demonstrated peak-stimulated GH remained significantly associated with LDL particle size (ß = 0·01; P = 0·01; R(2) = 0·42; P < 0·0001 for overall model) and HDL particle size (ß = 0·008; P = 0·001; R(2) = 0·44; P < 0·0001 for overall model). CONCLUSIONS: These results suggest reduced peak-stimulated GH in obesity is independently associated with a more atherogenic lipoprotein profile defined in terms of particle size.

Increased skeletal muscle phosphocreatine recovery after sub-maximal exercise is associated with increased carotid intima-media thickness.

BACKGROUND: The association between skeletal muscle mitochondrial function and CVD risk in healthy subjects is unknown. METHODS: Forty subjects were evaluated for CVD risk with lipid profile, oral glucose tolerance test and measurement of carotid intima-media thickness (cIMT). Skeletal muscle mitochondrial function was determined by phosphocreatine recovery after sub-maximal exercise with (31)Phosphorous-MRS and represented as τPCr. RESULTS: τPCr was positively associated with age (r=+0.41; P=0.009) and cIMT (r=+0.50; P=0.001) on univariate analyses. In multivariate regression analysis controlling for age, the association between τPCr and cIMT remained significant (ß=0.003; P=0.03). This association remained significant after controlling for traditional risk factors for CVD including age, gender, tobacco use, BMI, blood pressure, cholesterol and fasting glucose in a combined model (ß=0.003; P=0.04; R(2)=0.53; P=0.008 for overall model). CONCLUSIONS: These data suggest a novel association between skeletal muscle τPCr and increased cIMT, independent of age or traditional CVD risk factors.

The association of growth hormone parameters with skeletal muscle phosphocreatine recovery in adult men.

CONTEXT: Previous studies have suggested a relationship between GH and mitochondrial function. However, little is known about the relationship of specific GH indices and in vivo measures of mitochondrial function in humans. OBJECTIVE: The objective of this study was to determine the association between GH, IGF-I, and phosphocreatine (PCr) recovery, a measure of mitochondrial function, in otherwise healthy adults. DESIGN: Thirty-seven healthy men and women were studied at a single university medical center. Subjects underwent GH stimulation testing with GH releasing hormone-arginine and measurement of IGF-I. Mitochondrial function was determined by PCr recovery after submaximal exercise by (31)Phosphorous magnetic resonance spectroscopy. Subjects underwent assessment of lean and fat mass with use of dual energy X-ray absorptiometry. RESULTS: There were no differences in PCr recovery between men and women (men 20.7±1.5 vs. women 24.8±1.4 mM/min; P > 0.05). IGF-I (r = 0.33; P = 0.04) was associated with PCr recovery in all subjects. Among men, IGF-I (r = 0.69; P = 0.003), peak stimulated GH (r = 0.52; P = 0.04), and GH area under the curve (AUC) (r = 0.53; P = 0.04) were significantly associated with PCr recovery. However, neither IGF-I, peak stimulated GH, nor GH AUC (all P > 0.05) were associated with PCr recovery in women. After adjusting for age, race, and physical activity, IGF-I remained significantly associated with PCr recovery (ß = 0.10; P = 0.02) among men. CONCLUSIONS: IGF-I, peak stimulated GH, and GH AUC are associated with skeletal muscle PCr recovery in men.

The relationship between reduced testosterone, stimulated growth hormone secretion and increased carotid intima-media thickness in obese men.

OBJECTIVE: Obesity is associated with reduced testosterone and growth hormone (GH). However, the interrelationship between these axes and their independent contributions to cardiovascular risk is unknown. The objectives of this study were to determine (1) the association between testosterone and GH in obesity, (2) whether excess adiposity mediates this association and (3) the relative contribution of reduced testosterone and GH to increased carotid intima-media thickness (cIMT) in obesity. DESIGN: Fifty obese men were studied with GH-releasing hormone-arginine testing, and morning free testosterone (FT) was measured by equilibrium dialysis. Metabolic, anthropometric and cardiovascular risk indices, including cIMT were measured. Twenty-six normal weight men served as controls. RESULTS: Obese subjects demonstrated lower mean (±SEM) peak stimulated GH (5·9 ± 0·6 vs 36·4 ± 3·9 µg/l; P < 0·0001) and FT (0·41 ± 0·03 vs 0·56 ± 0·03 nmol/l; P = 0·0005) compared to controls. GH was significantly associated with FT (r = +0·44; P < 0·0001) and both were inversely related to visceral adipose tissue (VAT) (GH: r = -0·65; P < 0·0001; FT: r = -0·51; P < 0·0001). In multivariate regression analysis controlling for VAT, FT was no longer related to GH. Both GH and FT were associated with cIMT in univariate analysis. However, in multivariate modelling including traditional cardiovascular risk markers, GH (ß = 0·003; P = 0·04) but not FT (P = 0·35) was associated with cIMT. CONCLUSIONS: These results demonstrate a strong relationship between FT and GH in obesity and suggest that this relationship is more a function of excess adiposity rather than a direct relationship. While reduced FT and GH are both related to increased cIMT, the relationship with reduced GH remains significant controlling for reduced FT and traditional cardiovascular disease risk markers.

Skeletal muscle phosphocreatine recovery after submaximal exercise in children and young and middle-aged adults.

CONTEXT: Elderly subjects have reduced mitochondrial function. However, it remains unclear whether the decline in mitochondrial function begins earlier in the life span. OBJECTIVE: The objective of the study was to determine skeletal muscle mitochondrial oxidative phosphorylation by (31)phosphorous-magnetic resonance spectroscopy (MRS) across a variety of age groups. DESIGN: This was a cross-sectional study of 121 healthy normal-weight and overweight individuals from age 8 to 55 yr. SETTING: The study was conducted at a single university medical center in Boston, MA. PARTICIPANTS: Participants included 68 children and 53 adults from the Boston community. INTERVENTIONS AND MAIN OUTCOME MEASURES: Phosphocreatine (PCr) recovery was evaluated by (31)phosphorous-MRS after submaximal exercise. Subjects were also evaluated with anthropometric measurements, metabolic profiles, and measures of physical activity. RESULTS: PCr recovery determined by (31)phosphorous-MRS is positively associated with age in univariate analysis in a cohort of individuals aged 8-55 yr (r = +0.55, P < 0.0001). Stratification of subjects into four age groups (prepubertal and early pubertal children, pubertal and postpubertal children < 18 yr, young adults aged 18-39 yr, and middle aged adults aged 40-55 yr) demonstrates prolongation of PCr recovery with increasing age across the four groups (P < 0.0001 by ANOVA). The relationship between PCr recovery and age remains strong when controlling for gender; race; ethnicity; body mass index; measures of physical activity and inactivity; and anthropometric, nutritional, and metabolic parameters (P < 0.004). CONCLUSIONS: Skeletal muscle PCr recovery measured by (31)phosphorous-MRS is prolonged with age, even in children and young adults.