Carbohydrate and lipid metabolism during various growth hormone dosing regimens in girls with Turner syndrome

To analyze the effects of supraphysiological dosages of growth hormone (GH) on carbohydrate (CHI and lipid metabolism, we investigated 87 girls with T urner syndrome (TS) in two studies: (1) a 4-year GH dose-response (DR) stud y comparing three groups with stepwise GH dosage increases up to 8 IU/m(2)/ d in girls aged 2 to 11 years, and (2) a 2-year GH administration frequency -response (FR) study in girls aged 11 to 17 years, comparing once-daily (OD ) and twice-daily [BID) injections of a total GH dose of 6 IU/m(2)/d in com bination with low-dose ethinyl estradiol (50 ng/kg/d orally). At baseline, impaired glucose tolerance (IGT) was present in 6% of the girls, and at the end of the studies, in 5%. In the DR study, the area under the curve for t ime-concentration (AUC(ab)) for glucose after an oral glucose tolerance tes t (OGTT) showed no change over time and no significant difference between a ny of the study groups. However, in all three DR groups, the AUC(ab) for in sulin, fasting glucose, the insulinogenic index, hemoglobin A(1c) (HbA(1c)) , and urinary C-peptide (uCp) were all significantly higher after 4 years c ompared with pretreatment (P<.05). In the FR study, group differences were not observed. Compared with healthy Dutch control subjects, the median base line levels in relatively young girls in the DR study were similar for tota l cholesterol (TC) and lower for high-density lipoprotein (HDL) cholesterol . In contrast, the median TC revels of relatively older girls in the FR stu dy were higher and HDL levels were similar. With increasing GH dosage in th e DR study, median TC and low-density lipoprotein (LDL) levels decreased, w hereas median HDL levels increased. The changes after 4 years were signific ant, including a decrease in the atherogenic index. GH treatment at the sup raphysiological dosages used in this study did not increase the frequency o f IGT or clinical diabetes. However, we observed an increased insulinogenic index indicative of insulin resistance. Therefore, long-term follow-up stu dy is warranted in these otherwise healthy subjects. OD injection regimens changed the lipid profile toward a more cardioprotective direction with a s ignificant reduction of the TC/HDL cholesterol ratio. Copyright (C) 1999 by W.B. Saunders Company.