Improvement in insulin sensitivity without concomitant changes in body composition and cardiovascular risk markers following fixed administration of a very low growth hormone (GH) dose in adults with severe GH deficiency

Yuen, Kevin C.J.; Frystyk, Jan; White, Deborah; Twickler, Th.B.; Koppeschaar, H. P. F.; Harris, Philip E.; Fryklund, Linda; Murgatroyd, Peter R.; Dunger, David B.

doi:10.1111/j.1365-2265.2005.02359.x

Cited by 61 publications

(48 citation statements)

References 66 publications

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“…Insulin concentrations and the HOMA-IR index increased after GH replacement in our patients, although no changes were observed in fasting plasma glucose. Recently, some authors found no changes or impairment in insulin sensitivity after short-term GH treatment (11,12) while, in contrast to our findings, other reports described an improvement in insulin sensitivity after GH therapy (10,23). No relationship between PAPP-A and glucose homeostasis parameters was found in our patients.…”

Section: Discussioncontrasting

confidence: 99%

“…Highly sensitive C-reactive protein (hsCRP), an acute-phase protein produced predominantly by hepatocytes under the influence of cytokines, such as interleukin-6 (IL-6), has been validated as one of the best cardiovascular risk markers (21). Some studies have demonstrated that GH replacement in GHD adults has beneficial effects on peripheral markers of inflammatory activity such as plasma hsCRP, IL-6 and fibrinogen (22)(23)(24).…”

Section: Introductionmentioning

confidence: 99%

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Effects of GH treatment in GH-deficient adults on adiponectin, leptin and pregnancy-associated plasma protein-A.

Joaquín

Aguilera²,

Granada³

et al. 2008

European Journal of Endocrinology

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Objective: GH deficiency (GHD) in adults is associated with adverse effects on metabolism and increased cardiovascular risk. Pregnancy-associated plasma protein-A (PAPP-A) is a protease that promotes IGF-I availability in vascular tissues. PAPP-A levels appear to correlate with carotid intima-media thickness and have been proposed as an early predictor of cardiac events. The aim of our study was to evaluate PAPP-A levels in GHD adults at baseline and after GH replacement and correlate them with changes in body composition, lipid profile, glucose homeostasis, inflammatory markers and in leptin and adiponectin. Patients and methods: Fourteen GHD adults were evaluated at baseline and after 1 year of GH therapy. All patients were compared at baseline with 28 age-, sex-and body mass index (BMI)-matched control subjects. Results: At baseline, GHD adults showed higher PAPP-A levels (PZ0.03) and higher leptin (PZ0.04), fibrinogen (PZ0.002) and highly sensitive C-reactive protein (PZ0.01) values than controls. Therapy with GH reduced PAPP-A (PZ0.03) and fibrinogen levels (PZ0.002) while increased BMI (PZ0.01) and reduced waist-hip ratio (WHR; PZ0.05) were observed. Insulin and homeostasis model assessment of insulin resistance index increased after treatment (P!0.004/PZ0.007), without changes in leptin or adiponectin levels. PAPP-A values correlated positively with BMI and WHR and negatively with adiponectin before and after treatment, with no correlation with glucose homeostasis parameters, lipid profile or leptin. Conclusions: Our study suggests that PAPP-A expression is increased in GHD adults, and that 1 year of GH replacement therapy is able to reduce PAPP-A levels in this population. However, further studies are required to determine whether this decrease correlates with an improvement in atherosclerosis.European Journal of Endocrinology 158 483-490

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of GH treatment in GH-deficient adults on adiponectin, leptin and pregnancy-associated plasma protein-A.

Joaquín

Aguilera²,

Granada³

et al. 2008

European Journal of Endocrinology

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“…However, as IGF-I levels are determined by insulin secretion (Holly et al 1989), cause and effect may be difficult to identify, yet IGF-I may be a determinant of insulin secretion (Kulkarni et al 2002;Xuan et al 2002). This hypothesis can be tested and aetiological trials are currently being carried out in the MRC Ely cohort to look at the effects of low-dose growth hormone, which lead to small increases in IGF-I levels (Yuen et al 2005), on insulin secretion and the risk for the development of impaired glucose tolerance (Yuen et al 2004).…”

Section: Maintenance Of B-cell Massmentioning

confidence: 99%

Session 7: Early nutrition and later health Early developmental pathways of obesity and diabetes risk

2007

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Size at birth and patterns of postnatal weight gain have been associated with adult risk for the development of type 2 diabetes in many populations, but the putative pathophysiological link remains unknown. Studies of contemporary populations indicate that rapid infancy weight gain, which may follow fetal growth restriction, is an important risk factor for the development of childhood obesity and insulin resistance. Data from the Avon Longitudinal Study of Pregnancy and Childhood shows that rapid catch-up weight gain can lead to the development of insulin resistance, as early as 1 year of age, in association with increasing accumulation of central abdominal fat mass. In contrast, the disposition index, which reflects the β-cells ability to maintain insulin secretion in the face of increasing insulin resistance, is much more closely related to ponderal index at birth than postnatal catch-up weight gain. Infants with the lowest ponderal index at birth show a reduced disposition index at aged 8 years associated with increases in fasting NEFA levels. The disposition index is also closely related to childhood height gain and insulin-like growth factor-I (IGF-I) levels; reduced insulin secretory capacity being associated with reduced statural growth, and relatively short stature with reduced IGF-I levels at age 8 years. IGF-I may have an important role in the maintenance of β-cell mass, as demonstrated by recent studies of pancreatic β-cell IGF-I receptor knock-out and adult observational studies indicating that low IGF-I levels are predictive of subsequent risk for the development of type 2 diabetes. However, as insulin secretion is an important determinant of IGF-I levels, cause and effect may be difficult to establish. In conclusion, although rapid infancy weight gain and increasing rates of childhood obesity will increase the risk for the development of insulin resistance, prenatal and postnatal determinants of β-cell mass may ultimately be the most important determinants of an individual's ability to maintain insulin secretion in the face of increasing insulin resistance, and thus risk for the development of type 2 diabetes.

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“…Withdrawal from such treatment could therefore be beneficial and account for some of the cardiovascular variables that are improved after 60-month observation. Recently, it has been reported that GH treatment in very low dose (approximately onetenth of the one we have used) enhances insulin sensitivity with no apparent effects on body composition, lipolysis, and other surrogate cardiovascular risk markers in adults with severe acquired GHD (28). Lowdose short-acting GH regimen could have different vascular effects.…”

Section: Discussionmentioning

confidence: 99%

Arrest of atherosclerosis progression after interruption of GH replacement in adults with congenital isolated GH deficiency

Araújo

Aguiar‐Oliveira

Oliveira

et al. 2012

European Journal of Endocrinology

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Objective: GH replacement therapy (GHRT) in adult-onset GH deficiency (AOGHD) reduces carotid intima-media thickness (IMT) and increases myocardial mass, with improvement of systolic and diastolic function. These observations have reinforced the use of GHRT on AOGHD. Conversely, we have previously reported that in adults with lifetime congenital and severe isolated GH deficiency (IGHD) due to a mutation in GHRH receptor gene (GHRHR), a 6-month treatment with depot GH increased carotid IMT, caused the development of atherosclerotic plaques, and an increase in left ventricular mass index (LVMI), posterior wall, and septal thickness and ejection fraction. Such effects persisted 12 months after treatment (12-month washout -12mo). Methods: We have studied the cardiovascular status (by echocardiography and carotid ultrasonography) of these subjects 60 months after completion of therapy (60-month washout -60mo). Results: Carotid IMT reduced significantly from 12 to 60mo, returning to baseline (pre-therapy) value. The number of individuals with plaques was similar at 12 and 60mo, remaining higher than pretherapy. LVMI, relative posterior wall thickness, and septum thickness did not change between 12 and 60mo, but absolute posterior wall increased from 12 to 60mo. Systolic function, evaluated by ejection fraction and shortening fraction, was reduced at 60mo in comparison with 12mo returning to baseline levels. The E/A wave ratio (expression of diastolic function) decreased at 60mo compared with both 12mo and baseline. Conclusions: In adults with lifetime congenital IGHD, the increase in carotid IMT elicited by GHRT was transitory and returned to baseline 5 years after therapy discontinuation. Despite this, the number of subjects with plaques remained stable at 60mo and higher than at baseline. 166 977-982 European Journal of Endocrinology

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Improvement in insulin sensitivity without concomitant changes in body composition and cardiovascular risk markers following fixed administration of a very low growth hormone (GH) dose in adults with severe GH deficiency

Cited by 61 publications

References 66 publications

Effects of GH treatment in GH-deficient adults on adiponectin, leptin and pregnancy-associated plasma protein-A.

Effects of GH treatment in GH-deficient adults on adiponectin, leptin and pregnancy-associated plasma protein-A.

Session 7: Early nutrition and later health Early developmental pathways of obesity and diabetes risk

Arrest of atherosclerosis progression after interruption of GH replacement in adults with congenital isolated GH deficiency

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