Ann Pediatr Endocrinol Metab > Volume 22(3); 2017 > Article |
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Study | Number of GHD cases | Age (yr) | Daily GH dose | Duration of GHT | Findings |
---|---|---|---|---|---|
High dose | |||||
Fowelin et al. [35] | 9 | 38–63 | 0.023 mg/kg | 6 Weeks | ↑Fasting glucose, ↑insulin, ↓IS (EC) |
26 Weeks | ↔Fasting glucose, ↔insulin, ↓IS (EC) | ||||
Chipman et al. [36] | AO (rhGH=52, P=46) | 43.5±9.8 | 0.012 mg/kg | 6 Months | ↑Fasting glucose, ↔insulin, ↔HbA1c |
18 Months | ↔Fasting glucose, ↔insulin, ↔HbA1c | ||||
CO (rhGH=32, P=35) | 28.4±7.2 | 0.012 mg/kg | 6 Months | ↑Fasting glucose, ↑insulin, ↔HbA1c | |
18 Months | ↔Fasting glucose, ↔insulin, ↔HbA1c | ||||
Hwu et al. [21] | rhGH=7, P=9 | 20–44 | 0.011 mg/kg | 6 Months | ↔Fasting glucose, ↔IS (MIST) |
12 Months | ↔Fasting glucose, ↓IS (MIST) | ||||
Christopher et al. [37] | rhGH=7, P=7 | 43.7±4.1 | 0.011 mg/kg | 6 Months | ↑Fasting glucose, ↔insulin, ↔HbA1c |
24 Months | ↔Fasting glucose,↑insulin, ↓IS (EC) | ||||
Rosenfalck et al. [22] | 11 | 26–57 | 0.016 mg/kg | 30 Months | ↑AUC gluc, ↑AUC insulin (OGTT), ↓IS (FSIGT) |
Sesmilo et al. [38] | rhGH=20, P=20 | 24–64 | 0.01 mg/kg | 6 Months | ↑Fasting glucose,↑insulin, ↔HbA1c |
18 Months | ↑Fasting glucose, ↔insulin, ↔HbA1c | ||||
Chrisoulidou et al. [39] | rhGH=12, C=21 | 52±10 | 0.7 mg | 7 Years | ↔Fating glucose, ↔insulin, ↔AUC gluc, ↑AUC insulin (OGTT) |
Giavoli et al. [40] | 20 | 44±14 | 0.01–0.024 mg/kg | 1 Year | ↑Fasting gluose, ↑HOMA-IR, ↓QUICKI |
5 Years | ↑Fasting gluose, ↔HOMA-IR, ↔QUICKI | ||||
Low dose | |||||
al-Shoumer et al. [41] | 13 | 24–65 | 0.008 mg/kg | 1 Year | ↑Fasting gluose, ↑AUC gluc,↑AUC insulin (OGTT) |
4 Years | ↔Fasting glucose, ↔AUC gluc, ↔AUC insulin (OGTT) | ||||
Gibney et al. [42] | rhGH=10, P=11 | 21–51 | 0.008 mg/kg | 10 Years | ↔Fasting glucose, ↔insulin, ↔c-peptide |
Svensson et al. [43] | 11 | 52±3.9 | 0.61 mg | 7 Years | ↔Fasting glucose, ↔insulin, ↔IS (EC) |
Bramnert et al. [44] | rhGH=10, P=9 | 42±2.6 | 0.009 mg/kg | 1 Week | ↑Fasting glucose, ↑insulin, ↓IS (EC) |
6 Months | ↑Fasting glucose, ↑insulin, ↓IS (EC) | ||||
Yuen et al. [25] | 8 | 32–59 | 0.1 mg | 12 Months | ↓Fasting glucose, ↔insulin, ↑HOMA-S |
8 | 31–60 | 0.5 mg | ↔Fasting glucose, ↔insulin, ↔HOMA-S | ||
Roemmler et al. [45] | rhGH=22, C=30 | 27–82 | 0.30 mg | 2–42 Years (mean 11) | ↓Fasting glucose, ↔insulin, ↔HOMA-IR, ↔HbA1c, ↔AUC gluc, ↔AUC insulin, ↔IS (OGTT) |
Woodmansee et al. [23] | No DM (rhGH=337, C=134) | 48.9±0.7 | 0.36 mg | 2.33±1.34 Years | ↔IFG (>109 mg/dL), ↔HbA1c |
DM (rhGH=64, C=35) | 56.0±1.7 | ↔IFG (>109 mg/dL), ↔HbA1c | |||
Elbornsson et al. [24] | 156 | 22-74 | 0.40 mg | 15 Years | ↑Fasting glucose (year 1–year 10), ↓HbA1c (year 7–year 15) |
Yuen and Dunger [26] | rhGH=8, C=9 | 46±3.7 | 0.005 mg/kg | 3 Months | ↔Fasting glucose, ↔insulin, ↑IS (EC) |
Weber et al. [46] | 245 | 49±14 | 0.37 mg | 4 Years | ↔Fasting glucose, ↔HbA |
Participant’s age was presented in mean±standard deviation or range.
GH, growth hormone; GHD, growth hormone deficiency; GHT, growth hormone treatment; IS, insulin sensitivity; EC, euglycemic clamp; AO, adult onset; HbA1c, glycosylated hemoglobin; CO, childhood onset; rhGH, recombinant human growth hormone; MIST, modified insulin suppression test; HOMA-IR, homeostasis model assessment of insulin resistance; AUC gluc, the area under the curve for glucose; AUC insulin, the area under the curve for insulin; OGTT, oral glucose tolerance test; P, placebo; FSIGT, frequently-sampled intravenous glucose tolerance test; QUICKI, quantitative insulin check index; HOMA-S, homeostasis model assessment of insulin sensitivity.
Study | Number of cases | Age (yr) | Daily GH dose | Duration of GHT | Findings |
---|---|---|---|---|---|
Attanasio et al. [47] | 2,922 in US, 3,709 in Europe | 45.4±15 | - | 4.1 Years | ↔DM prevalence (11.3% in US, 5.7% in Europe) |
↔DM incidence (n/1,000 patient-years: 14.1 in US, 7.0 in Europe) | |||||
Luger et al. [28] | 5,143 KIMS cohort | 49±13 | 0.36 mg | 3.9 Years | ↑DM incidence 26/1,000 patient-years |
Hartman et al. [27] | rhGH=1,988, control=442 | 46±15 | <0.012 mg/kg | 2.3 Years | ↔DM incidence |
Shimatsu et al. [48] | 209 in Japan | 18–64 | 0.25 mg | 2 Years | ↔DM incidence |
Study | Number of cases | Age (yr) | Daily GH dose | Duration of GHT | Findings |
---|---|---|---|---|---|
Saenger et al. [49] | GHD=70 | - | 0.05 mg/kg | 5 Years | ↔Fasting/postprandial glucose, ↑fasting/postprandial insulin, ↔HbA1c |
Heptulla et al. [29] | GHD=6, ISS=2 | 12±1 | 0.05 mg/kg | 6 Months | ↔Fasting glucose, ↑insulin, ↓IS (HC) |
Radetti et al. [50] | GHD=128, Healthy control=40 | 8.9±3.2 | 0.04–0.05 mg/kg | 6 Years | ↓QUICK, no cases with IGT, DM at 6 year |
Salerno et al. [51] | GHD=30, Healthy control=30 | 9.3±0.5 | 0.03 mg/kg | 2 Years | ↔Fasting glucose, ↑insulin, ↑HOMA-IR |
Metwalley et al. [52] | GHD=30, Healthy control=20 | 4–10 | 1 mg/m2 | 1 Year | ↑Fasting glucose, ↑insulin, ↑HOMA-IR |
Meazza et al. [53] | GHD=16, Healthy control=20 | 3.4–14.7 | 0.025 mg/kg | 1 Year | ↑Fasting glucose, ↑insulin |
Ramistella et al. [54] | GHD=32, Healthy control=33 | 8.9±3.6 | 0.03 mg/kg | 2 Years | ↔Fasting glucose, ↑insulin, ↑HOMA-IR |
Ciresi et al. [30] | GHD=73, Healthy control=50 | 10.3±2.8 | 0.025–0.033 mg/kg | 1 Year | ↔Fasting glucose, ↔insulin, ↑HOMA-IR, ↓QUICKI, ↔AUC gluc, ↓AUC insulin (OGTT),↓IS (HC) |
Participant’s age was presented in mean±standard deviation or range.
GH, growth hormone; GHT, growth hormone treatment; GHD, growth hormone deficiency; HbA1c, glycosylated hemoglobin; IS, insulin sensitivity; HC, hyperglycemic clamp; QUICKI, quantitative insulin check index; IGT, impaired glucose tolerance; DM, diabetes mellitus; HOMA-IR, homeostasis model assessment of insulin resistance; AUC gluc, the area under the curve for glucose; AUC insulin, the area under the curve for insulin; OGTT, oral glucose tolerance test.
Study | Number of cases | Age (yr) | Daily GH dose | Duration of GHT | Findings |
---|---|---|---|---|---|
Blethen et al. [31] | >19,000 NCGS cohort | 7.2–12.9 (at enrollment) | - | - | ↑DM incidence in subjects with identifiable risk factors |
Cutfield et al. [32] | 23,333 KIGS cohort | 10.3 (7.2–12.7) | 0.03 mg/kg (0.02–0.04) | 2.9 Years | ↑T2DM incidence in subjects with identifiable risk factors, ↔T1DM incidence |
Child et al. [33] | 11,686 GeNeSIS cohort | 10.2 (6.5–12.7) | 0.04 mg/kg (0.03–0.05) | 2.5 Years | ↑T2DM incidence in subjects with identifiable risk factors, ↔T1DM incidence |
Poidvin et al. [34] | 5,100 French SAGhE cohort (iGHD, ISS, SGA) | 20–44 | 0.03±0.01 mg/kg | 4 Years | ↔DM prevalence |
Participant’s age was presented in mean±standard deviation, median (interquartile range), or range.
GH, growth hormone; DM, diabetes mellitus; GHT, growth hormone treatment; NCGS, National Cooperative Growth Study; KIGS, Pharmacia and Upjohn International Growth Study; T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus; GeNeSIS, GH-treated patients in the Genetics and Neuroendocrinology of Short Stature International Study; SAGhE, Safety and Appropriateness of Growth Hormone Treatments in Europe; iGHD, isolated growth hormone deficiency; ISS, idiopathic short stature; SGA, small-for-gestational age.