Abstract
This systematic review and meta-analysis was performed to summarize the long-term (more than 6months) effect of growth hormone (GH) replacement therapy (GHRT) on glucose metabolism among adults growth hormone deficiency (AGHD) patients. 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 (6-12months and more than12 months) according to the length of follow-up. 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 6-12months 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 12months 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). Overall, the current meta-analysis demonstrated that GHRT with a shorter duration (6-12months) 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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