Growth Hormone Responses to Growth-Hormone-Releasing Hormone and Thyrotropin-Releasing Hormone in Diabetic Patients With and Without Retinopathy

Abstract

Growth hormone (GH) responses to growth-hormone-releasing hormone (GRH) and thyrotropin-releasing hormone (TRH) were studied in 17 diabetic patients. Ten patients (group 1) had retinopathy corresponding to stage III-V (Scott's classification), and the remaining seven patients (group 2) had no retinopathy despite longer duration of diabetes in comparison with the patients in group 1. There were no differences in age, percent of ideal body weight, and serum HbA1 levels between the two groups. Basal serum GH levels were 1.9 +/- 0.4 ng/ml (mean +/- SEM) in group 1, and not different from the values in group 2 (1.6 +/- 0.7 ng/ml). However, GH responses to synthetic human GRH-44 (1 micrograms/kg body wt, i.v. bolus) were significantly greater in group 1, as judged by the maximal response or integrated GH secretion after the administration of GRH. There were no differences in serum insulin-like growth factor I (IGF-I) levels between group 1 (262 +/- 35 ng/ml) and group 2 (232 +/- 30 ng/ml), and no significant correlation was found between serum IGF-I levels and GH responses to GRH in either of the two groups. Paradoxical GH responses to TRH (500 micrograms, i.v. bolus) were found in only one patient in each group. We have thus demonstrated that GH responses to GRH are more pronounced in diabetic patients with retinopathy than in patients without this complication, although it remains to be determined whether or not greater GH responses to GRH are causally related to the development of diabetic retinopathy.

Peptide Hormone Regulation of Angiogenesis

“…The contribution of the GH/IGF-I axis to the pathophysiology of diabetic retinopathy (180,612) was described nearly four decades ago based on the elevated circulating GH levels found in diabetic subjects (275,445,497), the halted progression of diabetic retinopathy after anterior pituitary ablation (335) or radiation (496), and the reduced incidence of the disease in GH-deficient diabetic patients (14). Moreover, evidence that IGF-I reverses protection by a GH antagonist against ischemiainduced retinopathy (510), promotes VEGF-mediated retinal angiogenesis (443,511), and induces most of the alterations seen in diabetic retinopathy (475) substantiates the causative role of the GH/IGF-I axis in the development of the disease.…”

Effect of Growth Hormone-Releasing Hormone and Clonidine on Growth Hormone Release in Type 1 Diabetic Patients

“…Thus, Richards et al (1984) andPress et al (1984 in poorly controlled Type 1 diabetic subjects found a GH response to GHRH which was normal in absolute terms, but was considered to be "inappropriate" for the prevailing plasma glucose levels. On the other hand, Sharp et al (1984b) recorded in fasting hyperglycemic insulin-dependent patients with retinopathy a GH response which tended to be reduced, whereas Kaneko et al (1985) observed in normoglycemic retinopathic diabetic subjects a GH response to GHRH significantly higher than in normal subjects. GH hyperresponsiveness to GHRH has also been reported in streptozotocindiabetic rats (Locatelli, Miyoshi, Bestetti, Rossi and Miiller 1985).…”

“…GHRH, was characterized, studies on pituitary sensitivity to GHRH have been performed in both normal (Sharp et al 1984a;Masuda et al 1985) and diabetic subjects (Press et al 1984;Richards et al 1984;Sharp et al 1984b;Kaneko et al 1985).…”

“…Data derived from recent papers on the GH response to GHRH in diabetics are not conclusive (Press, Tamborlane, Thorner, Vale, Rivier, Gertner and Sherwin 1984;Richards, Wood, Christofides, Bhuttacharji and Bloom 1984;Sharp, Foley, Chahal andKohner 1984b;Kaneko, Komine, Maeda, Ohta, Tsushima and Shizume 1985), likely because of the heterogeneity and non-comparable metabolic conditions of the patients investigated.…”

Novel Approaches in the Treatment of Angiogenic Eye Disease

“…Several studies revealed only a weak or rather no association between IGF-I and diabetic retinopathy. For example no relationship was found between diabetic retinopathy and plasma IGF-I levels [65], serum IGF-I levels [66][67][68][69][70][71] or vitreous free IGF-I levels (in this case after adjusting for total intravitreous protein concentration) [72]. Nevertheless, in states of elevated IGF-I levels such as pregnancy and puberty, a progression of retinopathy was demonstrated [73][74][75].…”