Insulin-like growth factors and binding proteins in patients with recent-onset type 1 (insulin-dependent) diabetes mellitus: Influence of diabetes control and intraportal insulin infusion

Shishko, P. I.; Dreval, Alexander; Abugova, I. A.; Zajarny, I. U.; Goncharov, Valentin C.

doi:10.1016/0168-8227(94)90155-4

Cited by 73 publications

(58 citation statements)

References 39 publications

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“…The effects of restoring portal insulin levels on serum IGF1 have been studied in type I diabetes (49). Only with portal insulin administration, did IGF1 levels increase to within the normal range, which resulted in a decrease in GH levels.…”

Section: Lessons From Diabetes Type I and Iimentioning

confidence: 99%

Hypothesis: Extra-hepatic acromegaly: a new paradigm?

Neggers

Kopchick

Jørgensen

et al. 2011

European Journal of Endocrinology

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Medical treatment of acromegaly with long-acting somatostatin analogs (LA-SMSA) and the GH receptor antagonist, pegvisomant (PEGV), has made it possible to achieve normal serum IGF1 concentrations in a majority of patients with acromegaly. These two compounds, however, impact the GH-IGF1 axis differently, which challenges the traditional biochemical assessment of the therapeutic response. We postulate that LA-SMSA in certain patients normalizes serum IGF1 levels in the presence of elevated GH actions in extra-hepatic tissues. This may result in persistent disease activity for which we propose the term extra-hepatic acromegaly. PEGV, on the other hand, blocks systemic GH actions, which are not necessarily reliably reflected by serum IGF1 levels, and this treatment causes a further elevation of serum GH levels. Medical treatment is therefore difficult to monitor with the traditional biomarkers. Moreover, the different modes of actions of LA-SMSA and PEGV make it attractive to use the two drugs in combination. We believe that it is time to challenge the existing concepts of treatment and monitoring of patients with acromegaly.

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Section: Lessons From Diabetes Type I and Iimentioning

confidence: 99%

Hypothesis: Extra-hepatic acromegaly: a new paradigm?

Neggers

Kopchick

Jørgensen

et al. 2011

European Journal of Endocrinology

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“…However, there are few studies on the relationship between glycaemic control and plasma concentrations of IGF-I in adult patients with type 1 diabetes. A negative relationship between glycaemic control and circulating IGF-I has been shown by some investigators (13,14,18) but not by others (19,20). In adult patients with type 1 diabetes with good glycaemic control and without endogenous production of insulin, the plasma concentrations of free insulin are normal or increased in the fasting state and between meals, whereas meal-related insulin peaks are low compared with those in non-diabetic control individuals (21).…”

Section: Introductionmentioning

confidence: 99%

Circulating IGF-I concentrations are low and not correlated to glycaemic control in adults with type 1 diabetes

Ekman¹,

Nyström²,

Arnqvist

2000

European Journal of Endocrinology

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Objective: To study plasma concentrations of insulin-like growth factor-I (IGF-I) in adults with type 1 diabetes (IDDM) in comparison with a reference population, and the in¯uence of glycaemic control, dose of insulin, and sex on the concentration of circulating IGF-I in IDDM. Design and methods: Patients with type 1 diabetes were recruited consecutively from our outpatient diabetes unit. In all, 79 men and 55 women aged 20±60 years with a disease duration $6 years (range 6±51 years) took part in the study. A reference population of 80 men and 83 women aged 20±60 years was randomly obtained from the population registry. IGF-I was measured with radioimmunoassay after acid±ethanol extraction.

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“…Restoring the portal insulin concentration in DM1 has an impact on IGF-1 serum concentration. 21 Only when insulin was replaced in the portal vein, IGF-1 level increased into the normal range and a decrease in GH levels. 21 When insulin was replaced subcutaneous, by continuous or intermitted administration, IGF-1 concentrations were low and GH levels were elevated.…”

mentioning

confidence: 99%

“…21 Only when insulin was replaced in the portal vein, IGF-1 level increased into the normal range and a decrease in GH levels. 21 When insulin was replaced subcutaneous, by continuous or intermitted administration, IGF-1 concentrations were low and GH levels were elevated. 21 Others reported on the effects of GH administration in DM1 patients with and without residual β-cell function, assessed by C-peptide.…”

mentioning

confidence: 99%

“…21 When insulin was replaced subcutaneous, by continuous or intermitted administration, IGF-1 concentrations were low and GH levels were elevated. 21 Others reported on the effects of GH administration in DM1 patients with and without residual β-cell function, assessed by C-peptide. 22 GH induced an increase in IGF-1 serum concentration only in the C-peptide positive group, DM1 with residual β-cell function.…”

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confidence: 99%

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Extra-hepatic Acromegaly

Franck¹,

Lely²,

Neggers³

2013

US Endocrinology

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Acromegaly is a rare disease and in majority of cases caused by a growth hormone (GH)-producing pituitary adenoma. More than 75 % of these adenomas are macroadenomas.1 Acromegaly is characterized by excessive skeletal growth, soft tissue enlargement and reduced quality of life. The cornerstone of the diagnosis acromegaly consists of insufficient GH suppression during oral glucose loading and elevated insulin-like growth factor-1 (IGF-1). Treatment is aimed at a reduction of sign and symptoms, improved quality of life, and a decrease in morbidity and mortality. AbstractAfter the introduction of somatostatin analogs (LA-SMSA) and the growth hormone (GH) receptor antagonist, pegvisomant (Peg-v) normal serum insulin-like growth factor-1 (IGF-1) concentrations in virtually every patients with acromegaly is possible. The impact of these products on the GH-IGF1 axis is completely different. We advocate that LA-SMSA may normalize serum IGF1 levels in the presence of elevated GH actions in extrahepatic tissues. This results in persistent peripheral disease activity that we call 'extra-hepatic acromegaly'. Peg-v competitively blocks systemic GH action and results in a GH serum level increase. Therefore high doses of Peg-v are necessary to control IGF-1. Since the mode of action differs between these products, it is questionable if identical IGF-1 levels, during Peg-v or LA-SMSA are really identical representations of the biochemical situation. With the traditional biomarkers medical treatment is therefore difficult to monitor with the traditional biomarkers. Additionally, Peg-v and LA-SMSA could be ideal combination since they have different mode of actions. We believe that the time has come to challenge the existing concepts of treatment and monitoring of patients with acromegaly. KeywordsAcromegaly, extra-hepatic acromegaly, somatostatin analogs, growth hormone receptor antagonist, Pegvisomant, growth hormone sensitivity, growth hormone deficiency, IGF-1 Additionally, LA-SMSA also decrease IGF-1 production in the rodent liver GH independently. 5 These factors might result in an underestimation of disease activity as IGF-I levels during LA-SMSA are already reduced by the GH independently effect of LA-SMSAs on IGF-1 concentration. When IGF-1 levels are within the normal range, clinicians might conclude that this is the result of direct GH suppressive effect of the LA-SMSA and thereby ignoring the GH independent effects on the liver IGF-1 production.However, other nonhepatic tissues, all with their own sensitivity to GH, like kidney, bone, and adipose tissues might still experience a relatively high GH action resulting in signs and symptoms. In this article we will describe these effects as the concept of 'extra-hepatic acromegaly'. 6 Similarities and Differences Between Actions of GH and IGF-1To further address extra-hepatic and hepatic acromegaly, a better understanding of the GH-IGF-1 axis in different metabolic situations is necessary. It is hard to address the individual effect of GH and IGF1 in psychologic condition...

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Insulin-like growth factors and binding proteins in patients with recent-onset type 1 (insulin-dependent) diabetes mellitus: Influence of diabetes control and intraportal insulin infusion

Cited by 73 publications

References 39 publications

Hypothesis: Extra-hepatic acromegaly: a new paradigm?

Hypothesis: Extra-hepatic acromegaly: a new paradigm?

Circulating IGF-I concentrations are low and not correlated to glycaemic control in adults with type 1 diabetes

Extra-hepatic Acromegaly

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