Metabolic parameters and adipokine profile during GH replacement therapy in children with GH deficiency.

OBJECTIVE: GH replacement therapy in children with GH deficiency (GHD) mainly promotes linear growth. Not only have very few studies fully analyzed the metabolic consequences of GH therapy, but also the question as to whether GH may affect adipokine secretion has been insufficiently investigated. Our aim was to study the effects of GH replacement therapy on auxological data, lipid and glycemic profiles, insulin homeostasis (HOMA-IR) and serum adipokines in children. METHODS: This was a 1-year prospective study. Thirty-four GHD children (11.6 +/- 2.6 years) and thirty healthy matched controls were enrolled. Children affected by GHD were studied both before beginning continuous GH replacement therapy and again at 12 months. RESULTS: At the beginning of the study, total and LDL cholesterol were higher in GHD children than in controls (P<0.001), whereas HDL cholesterol, triglycerides, insulin, HOMA-IR, leptin, and adiponectin were similar. At 12 months of continuous GH replacement therapy in the GHD group, there was a significant increase in both auxological data and IGF-I (P<0.001); total cholesterol (P<0.001), LDL (P<0.001), triglycerides (P<0.005), and leptin (P<0.001) decreased significantly; HDL (P<0.003), insulin (P<0.001), HOMA-IR (P<0.001) increased while adiponectin was unmodified. Furthermore, IGF-IDelta showed an inverse correlation with leptin Delta (rho = -0.398, P = 0.02). CONCLUSIONS: In GHD children, the evaluation of metabolic parameters proves to be a useful tool for the evaluation of auxological parameters during GH replacement therapy. In our study, GH replacement therapy in GHD children improved final height, restored IGF-I levels, reduced leptin levels, and improved the lipid profile, without producing any unfavorable effects on glucose metabolism.

Feedback inhibition of insulin secretion and insulin resistance in polycystic ovarian syndrome with and without obesity.

Hyperinsulinemia/insulin resistance is a well-known feature of polycystic ovarian (PCO) syndrome. In this study, the comparative roles of the peripheral tissues and the pancreatic beta-cells in its pathogenesis were evaluated. We determined basal serum C-peptide values (index of insulin secretion) and in vivo insulin action on peripheral glucose utilization (by the euglycemic hyperinsulinemic clamp technique) in obese (n = 5) and nonobese (n = 5) PCO women compared to obese (n = 5) and nonobese (n = 5) normal ovulatory women. During the clamp, feed-back inhibition of insulin on insulin secretion was studied by C-peptide percentage suppression. Serum C-peptide basal values did not differ significantly between the four groups. Insulin stimulated glucose utilization, expressed as M-value, was significantly decreased in both PCO groups compared to normal ovulatory women (p < 0.005). The metabolic clearance rate of glucose (MCR) and insulin (M/I) had the same behaviour. No differences were found between M, MCR and M/I values and the two groups of PCO subjects (obese/nonobese). The C-peptide percentage suppression was similar in all the groups. We conclude that PCO women have a significant insulin resistance that is independent of obesity, while basal and insulin-inhibited insulin secretion do not differ from normal-cycle subjects.

The influence of high dose intravenous immunoglobulins on immunological and metabolic pattern in newly diagnosed type I diabetic patients.

In autoimmune disease the functional deficiency of T suppressor cells, also described in Type I diabetes, may be restored through immunoglobulin (Ig) infusion, which increases antigen phagocytosis, NK activity, cell clones and antibody anti-idiotype responses. Sixteen Type I diabetic patients were studied: eight were treated soon after the initial correction of disease-onset glycemic deterioration with intensive intravenous (i.v.) 7S Ig treatment (0.4 g/kg/BW) for 1 week and once per week for 6 months, whilst the remaining patients constituted the control group. All patients were evaluated during the study for metabolic and immunological parameters. A reduction in insulin requirement compared to conventionally treated patients was observed at the third (0.17 +/- 0.06 vs 0.44 +/- 0.08 IU/kg/BW; P less than 0.02) and at the sixth month of therapy (0.19 +/- 0.07 vs 0.54 +/- 0.07 IU/kg/BW; P less than 0.005). Two patients ceased to require insulin therapy within the BW; P less than 0.005). Two patients ceased to require insulin therapy within the first month, showing a prolonged restoration of B-cell function. Serum C-peptide values were also significantly higher in the Ig-treated group compared to the control group after 3 and 6 months. As regards immunological parameters, patients showed a decrease in insulin antibody levels and a reduction in TAC+ cells. Intravenous Ig therapy seems able to affect positively the first phases of metabolic and immunological deterioration of Type I diabetes.