Increased insulin sensitivity in young, growth hormone deficient children

Husbands, Sandra; Ong, Ken K.; Gilbert, J. A. L.; Wass, John

doi:10.1046/j.1365-2265.2001.01298.x

Cited by 30 publications

(21 citation statements)

References 37 publications

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“…Our findings partially remind what is reported in young children with growth hormone deficiency, who show higher insulin sensitivity during childhood and teenage [38], develop insulin resistance at adult age [39] and show a transient and reversible hyperinsulinaemia during GHT [40]. …”

Section: Discussionsupporting

confidence: 69%

Effects of Growth Hormone Therapy on Glucose Metabolism and Insulin Sensitivity Indices in Prepubertal Children with Prader-Willi Syndrome

Crinò¹,

Giorgio²,

Manco

et al. 2007

Horm Res Paediatr

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In Prader-Willi syndrome (PWS) growth hormone therapy (GHT) improves height, body composition, agility and muscular strength. In such patients it is necessary to consider the potential diabetogenic effect of GHT, since they tend to develop type 2 diabetes, particularly after the pubertal age. The aim of our study was to investigate the effects of GHT on glucose and insulin homeostasis in PWS children. An oral glucose tolerance test (OGTT) was performed in 24 prepubertal PWS children (15 male, 9 female, age: 5.8 ± 2.8 years), 16 were obese (group A) and 8 had normal weight (group B), before and after 2.7 ± 1.3 years GHT (0.22 ± 0.03 mg/kg/week) and, only at baseline, in 35 prepubertal children with simple obesity (19 male, 16 female) (group C). Fasting glucose and insulin, glucose tolerance, insulin sensitivity index (ISI), homeostasis model assessment of insulin resistance (HOMA-IR), quick insulin check index (QUICKI), area under the curves (AUC) of glucose and insulin were estimated. At the start of GHT, all PWS children were normoglycaemic and normotolerant but two developed impaired glucose tolerance after 2.2 and 1.9 years of therapy, respectively. At baseline, group A showed lower fasting insulin levels, HOMA-IR and AUC of insulin, higher ISI, QUICKI and AUC of glucose than group C. Comparing groups A and B, AUC of insulin was higher and ISI lower in group A. During GHT, a significant increase of fasting insulin and glucose, a worsening of insulin resistance (HOMA-IR) and insulin sensitivity (QUICKI) was found only in group A while ISI did not change. The AUC of glucose decreased in both groups instead AUC of insulin did not change. BMI-SDS decreased in group A and increased in group B. The increased insulin resistance and decreased insulin sensitivity in obese PWS patients, as well as the occurrence of impaired glucose tolerance during GHT, suggest that a close monitoring of glucose and insulin homeostasis is mandatory, especially in treated obese PWS children.

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Section: Discussionsupporting

confidence: 69%

Effects of Growth Hormone Therapy on Glucose Metabolism and Insulin Sensitivity Indices in Prepubertal Children with Prader-Willi Syndrome

Crinò¹,

Giorgio²,

Manco

et al. 2007

Horm Res Paediatr

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show abstract

“…Do the adipocytes of GH-deficient animals reach a limit in their capacity to accumulate energy that would result in reduction of insulin sensitivity? We did not investigate this question; however, increased insulin sensitivity, despite obesity, is also observed in children with GH deficiency, an effect that diminishes with increasing age; paradoxically, GH-deficient adults demonstrate insulin resistance even before GH replacement therapy (43,44). Of note, too, is a recent study in lit/lit mice in which insulin sensitivity was analyzed up to 18 months of age; at age 12 months, lit/lit mice still had greater insulin sensitivity than control mice, but by age 18 months, they showed a blunted response to insulin (45).…”

Section: Discussionmentioning

confidence: 99%

Growth Hormone Regulation of p85α Expression and Phosphoinositide 3-Kinase Activity in Adipose Tissue

et al. 2007

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Phosphoinositide (PI) 3-kinase is involved in insulin-mediated effects on glucose uptake, lipid deposition, and adiponectin secretion from adipocytes. Genetic disruption of the p85␣ regulatory subunit of PI 3-kinase increases insulin sensitivity, whereas elevated p85␣ levels are associated with insulin resistance through PI 3-kinase-dependent and -independent mechanisms. Adipose tissue plays a critical role in the antagonistic effects of growth hormone (GH) on insulin actions on carbohydrate and lipid metabolism through changes in gene transcription. The objective of this study was to assess the role of the p85␣ subunit of PI 3-kinase and PI 3-kinase signaling in GH-mediated insulin resistance in adipose tissue. To do this, p85␣ mRNA and protein expression and insulin receptor substrate (IRS)-1-associated PI 3-kinase activity were measured in white adipose tissue (WAT) of mice with GH excess, deficiency, and sufficiency. Additional studies using 3T3-F442A cells were conducted to confirm direct effects of GH on free p85␣ protein abundance. We found that p85␣ expression 1) is decreased in WAT from mice with isolated GH deficiency, 2) is increased in WAT from mice with chronic GH excess, 3) is acutely upregulated in WAT from GH-deficient and -sufficient mice after GH administration, and 4) is directly upregulated by GH in 3T3-F442A adipocytes. The insulininduced increase in PI 3-kinase activity was robust in mice with GH deficiency, but not in mice with GH excess. In conclusion, GH regulates p85␣ expression and PI 3-kinase activity in WAT and provides a potential explanation for 1) the insulin hypersensitivity and associated obesity and hyperadiponectinemia of GH-deficient mice and 2) the insulin resistance and associated reduced fat mass and hypoadiponectinemia of mice with GH excess. Diabetes

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“…We must note that GH treatment in GH-deficient patients generally improves muscle strength, body composition, and exercise capacity, and thus produces positive consequences for the quality of life in humans [15]. Even though the reduction in insulin sensitivity during GH replacement was still evident in adult and children patients with GH deficiency [13,22], their competence to perform regular exercise was significantly enhanced by GH administration [15]. This improvement could have the benefit to allow patients increase their levels of physical activity for counterbalancing the GH-induced adverse effect in insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

Interactive Effect of Exercise Training and Growth Hormone Administration on Glucose Tolerance and Muscle GLUT4 Protein Expression in Rats

Hou¹,

Chou

Ho³

et al. 2003

J Biomed Sci

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The insulin-resistance effect of growth hormone (GH) administration has been frequently reported. The present study investigated the effect of GH administration on glucose tolerance and muscle GLUT4 protein expression in exercise-trained and untrained rats. Forty-eight rats were weight-matched and assigned to the following 4 groups: control, GH, exercise training, and exercise training + GH groups. After 2 weeks of GH injections (65 µg/kg/day) and exercise training, the glucose tolerance and insulin response were measured in these rats. The GLUT4 protein level, glycogen storage, and citrate synthase activity were determined in red gastrocnemius and plantaris muscles. Daily GH administration elevated the curves of the oral glucose tolerance test and insulin response compared with those of saline-injected control rats. Furthermore, exercise training completely eliminated this GH-induced insulin resistance as determined 18 h after the last bout of exercise training. Additionally, exercise training significantly increased muscle glycogen storage and GLUT4 protein levels. GH administration did not affect the GLUT4 protein and glycogen storage increases induced by exercise training, but the citrate synthase activity in the plantaris muscle was further elevated by GH administration to a level above that induced by training. In conclusion, this is the first study that demonstrates that regular exercise training prevents GH-induced insulin-resistance side effect in rats.

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Increased insulin sensitivity in young, growth hormone deficient children

Abstract: Young GH deficient children were more insulin sensitive than children with normal GH secretion. This difference attenuated with age and puberty, possibly secondary to pubertal sex steroids; however, insulin resistance as reported in GH deficient adults, was not observed in adolescents.

Cited by 30 publications

References 37 publications

Effects of Growth Hormone Therapy on Glucose Metabolism and Insulin Sensitivity Indices in Prepubertal Children with Prader-Willi Syndrome

Effects of Growth Hormone Therapy on Glucose Metabolism and Insulin Sensitivity Indices in Prepubertal Children with Prader-Willi Syndrome

Growth Hormone Regulation of p85α Expression and Phosphoinositide 3-Kinase Activity in Adipose Tissue

Interactive Effect of Exercise Training and Growth Hormone Administration on Glucose Tolerance and Muscle GLUT4 Protein Expression in Rats

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