He Zhou1, Lin Sun1, Siwen Zhang1, Yingxuan Wang1, Guixia Wang2. 1. Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, 130021, China. 2. Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, 130021, China. gwang168@jlu.edu.cn.
Abstract
PURPOSE: This systematic review and meta-analysis was performed to summarize the long-term (more than 6 months) effect of growth hormone (GH) replacement therapy (GHRT) on glucose metabolism among adults growth hormone deficiency (AGHD) patients. METHODS: We searched MEDLINE, EMBASE and the Cochrane Library databases from inception till March 2020 for relevant studies evaluating the effect of GHRT on glucose metabolism in AGHD patients. Results were stratified into two periods (6-12 months and more than12 months) according to the length of follow-up. RESULTS: Thirty-three studies including 11 randomized controlled trials (RCTs) and 22 prospective open-label studies (POLs) were included in the meta-analysis. The findings of this meta-analysis showed that GH supplementation with a duration of 6-12 months among adults with growth hormone deficiency (GHD) significantly increased fasting plasma glucose (FPG) (SMD 0.37; 95% CI 0.25 to 0.49; I2 = 0%; P < 0.00001), fasting insulin (FI) (SMD 0.2; 95% CI 0.08 to 0.33; I2 = 9%; P = 0.001), glycated hemoglobin (HbA1c) (SMD 0.31; 95% CI 0.17 to 0.46; I2 = 10%; P < 0.0001) and homeostasis model of assessment-insulin resistance (HOMA-IR) (SMD 0.28; 95% CI 0.08 to 0.47; I2 = 13%; P = 0.006). Notably, GH intervention with a duration of more than 12 months showed no significant effect on FI (SMD 0.14; 95% CI - 0.09 to 0.37; I2 = 0%; P = 0.24), HbA1c (SMD - 0.02; 95% CI - 0.3 to 0.26; I2 = 72%; P = 0.89) and HOMA-IR levels (SMD 0.04; 95% CI - 0.24 to 0.31; I2 = 0%; P = 0.80) in adults with GHD. However, FPG levels in AGHD were still significantly increased with more than one year intervention period (SMD 0.41; 95% CI 0.29 to 0.53; I2 = 0%; P < 0.00001). CONCLUSION: Overall, the current meta-analysis demonstrated that GHRT with a shorter duration (6-12 months) led to a deterioration in glucose metabolism including FPG, FI, HbA1c and HOMA-IR in AGHD patients. However, the negative effects of GH therapy on these glucose homeostasis parameters were not seen in longer duration of GHRT, except for FPG.
PURPOSE: This systematic review and meta-analysis was performed to summarize the long-term (more than 6 months) effect of growth hormone (GH) replacement therapy (GHRT) on glucose metabolism among adults growth hormone deficiency (AGHD) patients. METHODS: We searched MEDLINE, EMBASE and the Cochrane Library databases from inception till March 2020 for relevant studies evaluating the effect of GHRT on glucose metabolism in AGHD patients. Results were stratified into two periods (6-12 months and more than12 months) according to the length of follow-up. RESULTS: Thirty-three studies including 11 randomized controlled trials (RCTs) and 22 prospective open-label studies (POLs) were included in the meta-analysis. The findings of this meta-analysis showed that GH supplementation with a duration of 6-12 months among adults with growth hormone deficiency (GHD) significantly increased fasting plasma glucose (FPG) (SMD 0.37; 95% CI 0.25 to 0.49; I2 = 0%; P < 0.00001), fasting insulin (FI) (SMD 0.2; 95% CI 0.08 to 0.33; I2 = 9%; P = 0.001), glycated hemoglobin (HbA1c) (SMD 0.31; 95% CI 0.17 to 0.46; I2 = 10%; P < 0.0001) and homeostasis model of assessment-insulin resistance (HOMA-IR) (SMD 0.28; 95% CI 0.08 to 0.47; I2 = 13%; P = 0.006). Notably, GH intervention with a duration of more than 12 months showed no significant effect on FI (SMD 0.14; 95% CI - 0.09 to 0.37; I2 = 0%; P = 0.24), HbA1c (SMD - 0.02; 95% CI - 0.3 to 0.26; I2 = 72%; P = 0.89) and HOMA-IR levels (SMD 0.04; 95% CI - 0.24 to 0.31; I2 = 0%; P = 0.80) in adults with GHD. However, FPG levels in AGHD were still significantly increased with more than one year intervention period (SMD 0.41; 95% CI 0.29 to 0.53; I2 = 0%; P < 0.00001). CONCLUSION: Overall, the current meta-analysis demonstrated that GHRT with a shorter duration (6-12 months) led to a deterioration in glucose metabolism including FPG, FI, HbA1c and HOMA-IR in AGHD patients. However, the negative effects of GH therapy on these glucose homeostasis parameters were not seen in longer duration of GHRT, except for FPG.
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