Abstract
Impaired insulin sensitivity (IS) and β-cell dysfunction result in hyperglycaemia in patients of acromegaly. However, alterations in incretins and their impact on glucose-insulin homeostasis in these patients still remain elusive. Twenty patients of active acromegaly (10 each, with and without diabetes) underwent hyperinsulinemic euglycaemic clamp and mixed meal test, before and after surgery, to measure indices of IS, β-cell function, GIP, GLP-1 and glucagon response. Immunohistochemistry (IHC) for GIP and GLP-1 was also done on intestinal biopsies of all acromegalics and healthy controls. Patients of acromegaly, irrespective of presence or absence of hyperglycaemia, had similar degree of insulin resistance, however patients with diabetes exhibited hyperglucagonemia, and compromised β-cell function despite significantly higher GIP levels. After surgery, indices of IS improved, GIP and glucagon levels decreased significantly in both the groups, while there was no significant change in indices of β-cell function in those with hyperglycaemia. IHC positivity for GIP, but not GLP-1, staining cells in duodenum and colon was significantly lower in acromegalics with diabetes as compared to healthy controls possibly because of high K-cell turnover. Chronic GH excess induces an equipoise insulin resistance in patients of acromegaly irrespective of their glycaemic status. Dysglycaemia in these patients is an outcome of β-cell dysfunction consequent to GIP resistance and hyperglucagonemia.
Highlights
Is characterized by chronic growth hormone (GH) excess and almost invariably is caused by a GH-secreting pituitary adenoma[1]
The present study demonstrated that the various indices of insulin sensitivity are reduced to comparable levels in patients of acromegaly irrespective of the presence or absence of hyperglycaemia
GH is a potent antagonist of the insulin action on carbohydrate metabolism and induces insulin resistance (IR) which is considered to be the major pathogenetic mechanism responsible for glucose intolerance seen in patients with acromegaly[4]
Summary
Is characterized by chronic growth hormone (GH) excess and almost invariably is caused by a GH-secreting pituitary adenoma[1]. Studies done in the past have shown that insulin sensitivity (IS) is reduced to comparable levels in patients of acromegaly with and without glucose intolerance, suggesting that a GH-mediated compensatory hyperfunction of pancreatic β-cells might counterbalance the reduced IS in patients with normal glucose tolerance, but not in those with diabetes[22]. The incretin hormones strongly influence the glucose-insulin homeostasis, they have not been explored extensively and little is known about their effect on carbohydrate metabolism in patients with acromegaly. Exploring the incretin-axis in patients with acromegaly will help us to understand the pathogenesis of glucose intolerance in these patients, it may help to manage them more effectively. Our study aimed to investigate the alterations in incretin axis in patients with active acromegaly both before and after surgery. We explored the correlation between the circulating levels of incretins with expression pattern of GIP and GLP-1 staining cells in the intestinal biopsies of these patients
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