High prevalence of hypovitaminosis D in Sicilian children affected by growth hormone deficiency and its improvement after 12 months of replacement treatment.

PURPOSE: Although the correlation between vitamin D and growth hormone (GH)-insulin-like growth factor 1 (IGF1) axis is documented, as of date, few and conflicting studies have prospectively analyzed vitamin D before and after GH treatment. Our aim was to evaluate as to how the condition of GH deficiency (GHD) or GH treatment influences vitamin D in children. METHODS: Eighty Sicilian GHD children (M/F 58/22; mean age 10.3 years), grouped according to the season of evaluation in group A (June-September; 41 children) and group B (November-February; 39 children), were evaluated at baseline and after 12 months of GH treatment. RESULTS: Twenty-eight children (35 %) were vitamin D insufficient and 32 (40 %) deficient at baseline, and lower vitamin D levels were found in group B than in A (17.3 ± 5.3 vs. 31.1 ± 11.1 ng/ml; p < 0.001). A positive correlation between vitamin D and baseline GH levels (p < 0.001) was found. After 12 months, increased vitamin D was found both in all children (34.4 ± 16.4 vs. 24.5 ± 11.1 ng/ml; p = 0.002) and in group A (38.5 ± 14 vs. 31.1 ± 11.1 ng/ml; p < 0.001) and B (30 ± 17.7 vs. 17.3 ± 5.3 ng/ml; p < 0.001). Overall, only 25 (31 %) children remained insufficient and 15 (19 %) deficient, with an increase in prevalence of children with normal levels (p = 0.001). CONCLUSIONS: Our data demonstrated a very high prevalence of hypovitaminosis D in Sicilian GHD children, with an improvement after 12 months of GH treatment. Vitamin D assessment should therefore be considered routinely in GHD children both at diagnosis and during the follow-u

Reduction in insulin sensitivity and inadequate \u3b2-cell capacity to counteract the increase in insulin resistance in children with idiopathic growth hormone deficiency during 12 months of growth hormone treatment

Purpose: To evaluate the performance of various indexes of insulin sensitivity and secretion and to identify the most useful indicator of deterioration of glucose metabolism in a cohort of children with growth hormone (GH) deficiency (GHD) during GH treatment. Methods: In 73 GHD children (55 M, 18 F; mean age 10.5 years) at baseline and after 12 months of treatment, we evaluated a number of surrogate indexes of insulin secretion and sensitivity. In a subgroup of 11 children we also performed an euglycemic hyperinsulinemic clamp. Results: After 12 months, a significant increase in fasting glucose (p < 0.001) and HbA1c levels (p < 0.001) was documented, despite all children remained with a normal glucose tolerance. With regard the insulin secretion, Homa-\u3b2 did not show any significant change (p = 0.073), while oral disposition index (DIo) showed a significant decrease (p = 0.031). With regard the insulin sensitivity, Homa-IR significantly increased (p < 0.001) with a concomitant decrease in QUICKI (p < 0.001). ISI Matsuda showed a decrease, although not statistically significant (p = 0.069). In the subgroup of 11 children, the M value derived from clamp showed a significant decrease (p = 0.011) and a significant positive correlation was found between M value and ISI Matsuda both at baseline (\u3c1 0.950; p = 0.001) and after 12 months (\u3c1 0.980; p = 0.001) but not with Homa-IR and QUICKI. Conclusions: 12 months of GH treatment lead to a decrease in insulin sensitivity and impairment in insulin secretion relative to insulin sensitivity even without evident changes in glucose tolerance. DIo has proven to be the most useful indicator of deterioration of glucose metabolism even in cases in which the overt glucose abnormalities have not yet appeared

Comparison between euglycemic hyperinsulinemic clamp and surrogate indices of insulin sensitivity in children with growth hormone deficiency

Objective: Data about the impact of growth hormone treatment (GHT) on insulin sensitivity in children are quite controversial, due to the different surrogate indices that have been used. Design: We evaluated insulin sensitivity through the euglycemic hyperinsulinemic clamp, considered the gold standard technique, in 23 children affected by growth hormone deficiency (GHD) at baseline and after 12. months of GHT and in 12 controls with short stature at baseline, and we compared the clamp-derived index (M-value) with the most commonly used surrogate index of insulin sensitivity, as ISI Matsuda, and with circulating plasma markers of insulin sensitivity, as adiponectin and resistin levels. Results: At baseline, no significant difference in all metabolic parameters between GHD children and control subjects was found. After 12. months of GHT, GHD children showed a significant increase in fasting insulin (p <. 0.001) and resistin (p = 0.028) and a decrease in ISI Matsuda (p <. 0.001) and M-value (p. <. 0.001), without significant change in fasting glucose, HbA1c and adiponectin. In GHD children, M-value showed a significant but weak correlation with ISI Matsuda (rho 0.418, p = 0.047) at baseline, while no correlation with other parameters was found. After 12. months of GHT, M-value did not show any significant correlation with any other metabolic parameter analyzed. Conclusions: This study highlights the limit of the evaluation of insulin sensitivity performed through surrogate indices or circulating markers, which may lead to controversial data and do not correlate with the gold standard technique to evaluate insulin sensitivity

Visceral Adiposity Index Is Associated with Insulin Sensitivity and Adipocytokine Levels in Newly Diagnosed Acromegalic Patients.

Context: The visceral adiposity index (VAI) has proved to be a marker of visceral adipose dysfunction, strongly associated with insulin sensitivity in both the general and specific populations of patients at metabolic risk. Objective: The objective of the study was to test VAI as a useful tool to assess early metabolic risk in acromegaly. Patients: Twenty-four newly diagnosed acromegalic patients (11 women and 13 men, aged 54.9 ± 13.6 yr) were grouped into those with normal (group A, n = 13, 54.2%) and those with high VAI (group B, n = 11, 45.8%). Outcome Measures: Glucose, hemoglobin A1c, nadir and area under the curve (AUC) of GH (AUCGH) during the oral glucose tolerance test, AUCCpeptide during a mixed-meal tolerance test, M value during euglycemic-hyperinsulinemic clamp, oral dispositional index (DIo), each component of the metabolic syndrome, leptin, adiponectin, TNF-α, and IL-6. Results: The VAI value was positively correlated with the age of patients (ρ = 0.408; P = 0.048), tumor volume (ρ = 0.638; P = 0.001), basal GH (ρ = 0.622; P = 0.001), nadir GH (ρ = 0.534; P = 0.007), AUCGH (ρ = 0.603; P = 0.002), IGF-I (ρ = 0.618; P = 0.001), TNF-α (ρ = 0.512; P = 0.010), and AUCCpeptide (ρ = 0.715; p<0.001) and negatively with adiponectin (ρ = −0.766; P < 0.001), M value (ρ = −0.818; P < 0.001), and DIo (ρ = −0.512; P = 0.011). Patients with high VAI showed significantly higher basal GH levels (P = 0.018), AUCGH (P = 0.047), IGF-I (P = 0.047), AUCCpeptide (P = 0.018), lower M value (P < 0.001), DIo (P = 0.006), and adiponectin levels (P < 0.001), despite the absence of a significantly higher prevalence in the overt metabolic syndrome and glucose tolerance abnormalities. AUCGH proved to be the main independent factor influencing VAI. Conclusions: In acromegaly, VAI appears to be associated with disease activity, adiponectin levels, and insulin sensitivity and secretion and is influenced independently by GH levels. VAI could therefore be used as an easy and useful new tool in daily clinical practice for the assessment of early metabolic risk associated with active acromegal