**4.1 Growth hormone effect and treatment on the metabolism of carbohydrates**

Growth hormone (GH) therapy blocks insulin's effects on peripheral tissues such skeletal muscle, the liver, and adipose tissue, increasing glucose synthesis from these tissues and reducing adipose tissue glucose uptake [73]. Following GH injection, insulin synthesis is enhanced to counteract the elevated blood glucose. Chronic exposure to high FFA may have a direct harmful effect on beta cells due to GH-induced visceral adipose tissue lipolysis and the subsequent increase in circulating FFA [74]. Because IGF-1 mimics insulin in the liver and skeletal muscle, increasing its levels following GH injection may improve insulin resistance and glucose balance [75]. The effects of GH treatment on the glucose metabolism of the pediatric population have only been the subject of a modest number of studies. The majority of these studies have shown that increased insulin resistance, as shown by elevated fasting insulin and homeostasis model assessment of insulin resistance levels, was seen in GH-deficient children and adolescents during GH therapy, but their fasting/postprandial glucose and HbA1c levels remained within in normal range [76].

In individuals with GH deficiency, GH injection has been linked to a reduction in visceral adiposity and an improvement in cardio-metabolic dysfunction, according to a number of human investigations. While taking GH, certain studies have raised concerns about increased insulin resistance and impaired fasting glucose, particularly in obese and older patients. Studies on children and teenagers have suggested that GH injection may result in short-term treatment-induced insulin resistance, although its long-term effects have not yet been extensively analyzed [77]. It is advisable to monitor any potential detrimental effects on glucose metabolism both before and after GH delivery because international cohort studies indicate that GH therapy may increase the prevalence of type 2 diabetes mellitus in children and teens with predisposed risk factors. The long-term effects of GH therapy on cardiovascular outcomes in GH-deficient children with or without GH continuing following end of skeletal development require extensive longitudinal cohort studies [78].
