Changes of Carbohydrate Tolerance in Acromegaly with Progress of the Disease and in Response to Treatment

Ph, Sönksen; Greenwood, F. C.; Ellis, J. P.; Lowy, C.; Rutherford, Anne; Nabarro, J. D. N.

doi:10.1210/jcem-27-10-1418

Cited by 175 publications

(95 citation statements)

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“…Thus the results obtained are not at variance with the concept of tissue resistance to insulin action in states of chronic diabetogenic hormone excess, such as in acromegaly [38] and in Cushing's syndrome [39]. A possible influence of long-term exposure to insulin opposing hormones may be anticipated as a time-dependence has recently been demonstrated for growth hormone on lipid metabolism in insulin-withdrawn diabetics by Schade and Eaton [15].…”

Section: Discussionmentioning

confidence: 51%

The role of ?diabetogenic? hormones on carbohydrate and lipid metabolism following oral glucose loading in insulin dependent diabetics: Effects of acute hormone administration

et al. 1981

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Summary. To evaluate the relative role of "diabetogenic" hormones as insulin antagonists in severe derangements of diabetic control, glucagon, cortisol, growth hormone and adrenaline were administered by continuous intravenous infusion, separately and in combination, to ketosis-prone insulin-dependent diabetics (n = 11). The amount of insulin required for the assimilation of a 50 g glucose load during the various hormone infusions was determined by means of an automated glucose-controlled insulin infusion system and used as an index of insulin effectiveness. Raising plasma hormone concentrations acutely into the range seen in severe diabetic states (glucagon 517+_70pg/ml; cortisol 32-+3gg/dl; growth hormone 14+3ng/ml) did not alter significantly blood glucose profile and insulin requirement (control ll.3_l.lU; glucagon 11.6-+2.0U; cortisol 11.1_+0.4 U; growth hormone 12.9___1.4 U), except for adrenaline (plasma level 550_+ 192 pg/ml), which caused a marked rise in blood glucose levels and a threefold increase in insulin demand (31.1_+ 3.7 U). Combined infusion of all hormones did not potentiate significantly the latter effect (38.3___4.7 U). The effectiveness of metabolic control by insulin was assessed by a marked decrease in plasma nonesterified free fatty acids and ketone bodies upon its administration after glucose ingestion in all groups studied. It is concluded that from the hormones investigated within this study adrenaline exerts the strongest diabetogenic action during its short term administration followed by that of growth hormone. Whereas it may well be that over-insulinization of the patients by the glucose controlled insulin infusion system has overcome and disguised the smaller diabetogenic effects of cortisol and glucagon.Key words: Diabetes mellitus, counter-regulatory hormones, glucagon, cortisol, growth hormone, adrenaline, insulin, non-esterified fatty acids, ketone bodies.Excess secretion of insulin-counteracting hormones is claimed to be important in the metabolic changes and insulin resistance in diabetic ketoacidosis [1,2]. The observations in severe derangements of diabetic control include elevated plasma levels of glucagon [3], cortisol [4], growth hormone [5,6], and catecholamines [7,8]. The hierachy of their pathogenetic significance, however, remains to be established. Hyperglycaemia, decreased glucose tolerance and insulin resistance have been demonstrated under certain circumstances after exogenous administration of these hormones [9][10][11][12]. Furthermore, the above mentioned counter-regulatory hormones are known to exert lipolytic and ketogenic activity when elevated to high physiological concentrations in insulin deficient diabetic man [12][13][14][15][16]. The delay in the development of ketoacidosis in insulin-withdrawn diabetics by either somatostatin-induced suppression of growth hormone and glucagon [17] or following pituitary ablation [1] serves as further support for implicating these hormones as pathogenic factors of deranged metabolic control. In addition, circulator...

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Section: Discussionmentioning

confidence: 51%

The role of ?diabetogenic? hormones on carbohydrate and lipid metabolism following oral glucose loading in insulin dependent diabetics: Effects of acute hormone administration

et al. 1981

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“…Postoperatively, HOMA values decreased in all but one patient. An improvement of insulin resistance after surgery has been already observed for 30 years (40,53,54). This seems to be an advantage over the treatment with somatostatin analogues, which may counterbalance improvement of insulin resistance by their inhibitory effect on insulin secretion (55,56).…”

Section: Discussionmentioning

confidence: 97%

Effect of transsphenoidal surgery on sleep apnoea in acromegaly

Sze

Schmid²,

Bloch³

et al. 2007

eur j endocrinol

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Objective: Sleep apnoea syndrome (SAS) is common in acromegaly and both diseases are independently associated with hypertension and insulin resistance contributing to increased morbidity and mortality. Pituitary surgery remains the principal treatment modality in acromegaly. The aim of this study was to assess the prevalence and risk factors of SAS in acromegaly and to analyze the effect of transsphenoidal adenomectomy on SAS and cardiovascular risk factors. Subjects and methods: Thirteen consecutive patients (seven women and six men, aged 25-77 years) with newly diagnosed acromegaly were prospectively studied. Biochemical assessment (IGF-I, GH, acid labile subunit, fasting blood glucose (FBG), insulin), overnight respiratory polygraphy, and an Epworth Sleepiness scale score (ESS) were obtained before and 12 weeks after surgery. SAS was defined by an ESS R10 and R5 apnoeas/hypopnoeas (central or obstructive) per hour. Results: Six of the thirteen (46%) patients had SAS. Risk factors were male gender (83.3 vs 14.3% without SAS) and long disease duration until diagnosis of acromegaly (10.2G3.2 vs 4.6G3.6 years, meanGS.D.). Ten patients had a homeostasis assessment model score R4 indicating insulin resistance and one had diabetes mellitus requiring insulin. Seven patients had hypertension (R140/90 mmHg). Postoperatively, GH and IGF-I levels decreased, but only five patients were cured. However, SAS resolved in all patients irrespective of whether acromegaly was cured or not. FBG (5.5G1.2 vs 4.8G0.4 mmol/l) and systolic blood pressure (150.8G18.5 vs 130.8G17.5 mmHg) decreased in all SAS patients. Conclusion: We found a high prevalence of SAS in acromegaly patients, in particular, in men and those with long duration of disease. Importantly, a marked reduction of GH excess by transsphenoidal adenomectomy may cure SAS and improve insulin resistance and hypertension.European Journal of Endocrinology 156 321-329

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“…Impaired glucose tolerance (IGT) and overt type 2 diabetes mellitus (DM) are frequent findings in acromegalic patients, with a prevalence of the latter ranging from 19 to 56% (2,3,4,5).…”

Section: Introductionmentioning

confidence: 99%

Effects of medical therapies for acromegaly on glucose metabolism

Urbani

Sardella

Calevro

et al. 2013

European Journal of Endocrinology

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Objective: Abnormalities of glucose metabolism are common findings of acromegaly. However, robust evidence on whether therapy with somatostatin analogs (SSAs) or pegvisomant (PEG) differently affects glucose metabolism is lacking. The purpose of this study was to evaluate the effects of therapy with SSAs, PEG, or their combination on glucose metabolism in a large series of acromegalic patients. Design: This was a historical-prospective study. Among 50 consecutive acromegalic patients under SSA therapy, acromegaly in 19 patients was controlled. PEG used in combination with SSA therapy allowed the control of acromegaly in the remaining 31 patients and was then continued as monotherapy in 18 patients. Methods: The following parameters were evaluated at the diagnosis of acromegaly and during different treatments: fasting plasma glucose (FPG) and insulin concentrations, insulin sensitivity (QUICK-I), homeostasis model assessment of insulin resistance (HOMA2-IR), and plasma glucose and insulin concentrations during the oral glucose tolerance test (OGTT). Comparison was made using analysis for paired data. Results: Insulin resistance improved when acromegaly was controlled with therapy with SSAs, PEG, or SSACPEG. However, FPG concentrations were higher during SSA therapy (alone or combined with PEG) than at the diagnosis of acromegaly, even when corrected for disease activity, whereas they were reduced during PEG therapy. Mean glucose concentrations during the OGTT were higher in patients receiving SSA therapy than in those receiving PEG therapy. In addition, the prevalence of diabetes or impaired glucose tolerance was higher during SSA therapy than at diagnosis or during PEG therapy and was not influenced by disease control. Conclusions: Medical therapies for acromegaly reduce insulin resistance and increase insulin sensitivity; on the contrary, glucose indexes may be differently affected by SSA or PEG therapy.

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Changes of Carbohydrate Tolerance in Acromegaly with Progress of the Disease and in Response to Treatment

Cited by 175 publications

References 0 publications

The role of ?diabetogenic? hormones on carbohydrate and lipid metabolism following oral glucose loading in insulin dependent diabetics: Effects of acute hormone administration

The role of ?diabetogenic? hormones on carbohydrate and lipid metabolism following oral glucose loading in insulin dependent diabetics: Effects of acute hormone administration

Effect of transsphenoidal surgery on sleep apnoea in acromegaly

Effects of medical therapies for acromegaly on glucose metabolism

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