Growth hormone and its relationship to the microvascular complications of diabetes mellitus

Sharp, Patrick Stephen (1986) Growth hormone and its relationship to the microvascular complications of diabetes mellitus. MD thesis, University of Glasgow.

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The aim of this work was to discover possible causes of growth hormone (GH) hypersecretion in diabetic subjects, and to examine the possibility that the GH so produced is relevant to the development of diabetic microvascular disease. To reassess the hypothesis that GH plays a role in the genesis of diabetic microvascular complications, patients who had undergone pituitary ablation for treatment of retinopathy were followed up. Between 1960 and 1976, 117 patients had an pituitary implant. The 5 year mortality of these patients was 17.6% and the 10 year 51%, figures lower than generally reported for patients with proliferative retinopathy. Between 7 and 13% developed renal failure post-ablation, again lower than generally reported for unablated diabetics. The 100 patients operated on between 1965 and 1976 were included in the ophthalmological follow-up. Of these patients, the visual acuity in the better eye at the time of operation was 6/12 or more in 84%, this percentage remaining similar at the time of 5 and 10 year follow-up. By 5 years, grading of new vessels on the disc had improved from an initial grading of 2.7+1.6 to 0.8+1.2 (mean+SD, p<0.001), and by 10 years there was no disc neovascularisation in any eye. There was similar improvement in peripheral new vessels, hard exudates, microaneurysms and haemorrhages. It is concluded that pituitary ablation had a beneficial effect on the course of diabetic microvascular complications. After brief confirmation of the fact that GH hypersecretion can be demonstrated in patients with retinopathy using the 'in house' GH radioimmunoassay, an investigation of aspects of the GH regulatory pathways in normal and diabetic subjects was carried out to suggest potential causes of GH hypersecretion in diabetes. rising growth hormone releasing factor (1-44) (GRF), it is demonstrated that hyperglycaemia leads to a suppression of GRF stimulated GH secretion in normal subjects. Only 3 of 6 diabetic subjects studied in a similar fashion demonstrated suppression. In pituitary cells in culture, neither glucose nor insulin produced any effect on GRF stimulated GH secretion. It is concluded that hyperglycaemia produces suppression of GH by its action at hypothalamic level, and it can be inferred that there is a defect in GH regulation at this level in diabetes, perhaps mediated by lack of, or resistance to, somatostatin. Regarding the mechanism of GH hypersecretion in diabetes, 3 possible mechanisms are identified - somatostatin resistance induced by chronic hyperglycaemia, GH release induced by fluctuating plasma glucose, and failure of IGF-I generation secondary to poor glycaemic control. Regarding the role of GH and IGF-I in the genesis of diabetic microvascular complications, it is concluded that there is presently insufficient evidence to assign a specific role for either GH or IGF-I.

Item Type: Thesis (MD)
Qualification Level: Doctoral
Keywords: Medicine, Endocrinology
Date of Award: 1986
Depositing User: Enlighten Team
Unique ID: glathesis:1986-76642
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 19 Nov 2019 13:59
Last Modified: 19 Nov 2019 13:59

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