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Distinct metabolic surrogates predict basal and rebound GH secretion after glucose ingestion in men.

ABSTRACT: GH secretion declines rapidly after glucose ingestion and then recovers to higher-than-baseline levels (rebound GH release).Selective metabolic markers predict the magnitude of glucose-suppressed GH release and postglucose rebound-like GH secretion.Prospectively randomized crossover study of GH secretion after glucose vs. water ingestion.The study was conducted at a clinical translational research center.Sixty-nine healthy men aged 19-78 yr with a body mass index of 18-39 kg/m(2) participated in the study.OUTCOMES included nadir vs. peak GH concentrations and basal vs. pulsatile GH secretion.Mean nadir GH concentrations were determined positively by sex hormone binding globulin (SHBG) after glucose administration (R(2) = 0.088, P = 0.0077). Peak rebound GH concentrations were related positively to adiponectin and negatively to computed tomography-estimated abdominal visceral fat (AVF) (R(2) = 0.182, P = 0.00049) after glucose ingestion. Deconvolution analysis showed that SHBG specifically predicted basal (nonpulsatile) GH secretion after glucose exposure (R(2) = 0.153, P = 0.00052). In contrast, together exercise history and adiponectin (both positively) and AVF (negatively) predicted pulsatile GH escape after glucose suppression (R(2) = 0.206, P = 0.00043). Moreover, adiponectin uniquely determined the size (mass), and AVF the mode (duration), of GH secretory bursts after glucose exposure (both P < 0.006).Glucose ingestion provides a clinical model for investigating complementary metabolic surrogates that determine suppression and recovery of basal and pulsatile GH secretion in healthy men.

SUBMITTER: Iranmanesh A

PROVIDER: S-EPMC3387415 | biostudies-other | 2012 Jun

REPOSITORIES: biostudies-other

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Distinct metabolic surrogates predict basal and rebound GH secretion after glucose ingestion in men.

Iranmanesh Ali A Lawson Donna D Veldhuis Johannes D JD

The Journal of clinical endocrinology and metabolism 20120403 6

<h4>Context</h4>GH secretion declines rapidly after glucose ingestion and then recovers to higher-than-baseline levels (rebound GH release).<h4>Hypothesis</h4>Selective metabolic markers predict the magnitude of glucose-suppressed GH release and postglucose rebound-like GH secretion.<h4>Design</h4>Prospectively randomized crossover study of GH secretion after glucose vs. water ingestion.<h4>Setting</h4>The study was conducted at a clinical translational research center.<h4>Participants</h4>Sixty ...[more]

PMID: 22472562

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Project description:ObjectiveTo investigate the concordance/discordance of IGF-1 and peak stimulated GH in identifying subjects with reduced GH secretion and to determine the physiological significance of any discordance in obese subjects.Design, patients and methods95 obese and 43 normal weight men and women underwent measurement of IGF-1 and GH stimulation testing with GH releasing hormone (GHRH)-arginine. Reduced IGF-1 and GH secretion were defined using pre-determined cut-points. Cardiovascular disease risk was determined by measuring carotid intima-media thickness (cIMT). In a second study, IGF-1 was measured in 52 obese men and women who underwent GH stimulation testing and overnight frequent blood sampling. The association of IGF-1 and peak stimulated GH with parameters of endogenous GH secretion was assessed.Results60% of obese subjects had normal IGF-1 and peak stimulated GH while 8.4% of obese subjects had reduced IGF-1 and GH secretion. Discordance rate for IGF-1 and peak GH was 31.6%. Subjects with both low IGF-1 and low peak GH had the highest cIMT, while subjects with both normal IGF-1 and peak GH had the lowest cIMT. Subjects with reduction in either IGF-1 or peak GH, had intermediate cIMT (P=0.02). IGF-1 and peak stimulated GH were associated with maximum and mean overnight serum GH and GH AUC as well as maximum peak mass and median pulse mass. Peak stimulated GH, but not IGF-1, was also associated with nadir overnight serum GH concentration and basal GH secretion.ConclusionPeak stimulated GH and IGF-1 demonstrate significant discordance in identification of subjects with reduced GH secretion in obesity. Subjects with reduction of either IGF-1 or peak GH had higher cIMT compared to subjects with both normal IGF-1 and peak GH. Subjects with reductions in both IGF-1 and peak GH had the highest cIMT. Peak GH, compared to IGF-1, has broader associations with various parameters of endogenous GH secretion which support its utility in identifying those with reduced GH secretion.

Project description:Plasma viremia reoccurs in most HIV-infected individuals once antiretroviral therapy (ART) is interrupted. The kinetics of viral rebound, specifically the time until plasma virus becomes detectable, differ quite substantially between individuals, and associations with virological and immunological factors have been suggested. Standard clinical measures, like CD4 T-cell counts and plasma HIV RNA levels, however, are poor predictive markers. Antibody features, including Fc functionality and Fc glycosylation have been identified as sensitive surrogates for disease activity in multiple diseases. Here, we analyzed HIV-specific antibody quantities and qualitative differences like antibody-mediated functions, Fc gamma receptor (FcγR) binding, and IgG Fc glycosylation as well as cytokine profiles and cellular HIV DNA and RNA levels in 23 ART-suppressed individuals prior to undergoing an analytical ART interruption (ATI). We found that antibodies with distinct functional properties and Fc glycan signatures separated individuals into early and delayed viral rebounders (≤4 weeks versus >4 weeks) and tracked with levels of inflammatory cytokines and transcriptional activity of the viral reservoir. Specifically, individuals with early viral rebound exhibited higher levels of total HIV-specific IgGs carrying inflammatory Fc glycans, while delayed rebounders showed an enrichment of highly functional antibodies. Overall, only four features, including enhanced antibody-mediated NK cell activation in delayed rebounders, were necessary to discriminate the groups. These data suggest that antibody features can be used as sensitive indicators of HIV disease activity and could be included in future ATI studies.IMPORTANCE Plasma viremia reoccurs in most HIV-infected individuals once antiretroviral therapy is interrupted, and interindividual differences in the kinetics of viral rebound have been associated with virological and immunological factors. Antibody features, including Fc functionality and Fc glycosylation, have been identified as sensitive surrogates for disease activity in multiple diseases. Here, we systematically analyzed HIV-specific antibody quantities and qualitative differences in 23 ART-suppressed individuals prior to undergoing an analytical ART interruption (ATI). We found that antibodies with distinct functional properties and Fc glycan signatures separated individuals into early and delayed viral rebounders and tracked with levels of inflammatory cytokines and transcriptional activity of the viral reservoir. These data suggest that antibody features can be used as sensitive indicators of HIV disease activity and could be included in future HIV eradication studies.

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Distinct metabolic surrogates predict basal and rebound GH secretion after glucose ingestion in men.

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Distinct metabolic surrogates predict basal and rebound GH secretion after glucose ingestion in men.

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