Low Serum IGF-I/GH Ratio Is Associated with Abnormal Glucose Tolerance in Acromegaly

Fukuoka, Hidenori; Takahashi, Yutaka; Iida, Keiji; Kudo, Takumi; Nishizawa, Hitoshi; Imanaka, Mari; Takeno, Ryoko; Iguchi, Genzo; Takahashi, Kentaro; Okimura, Yasuhiko; Kaji, Hidesuke; Chihara, Kazuo

doi:10.1159/000112590

Cited by 10 publications

(14 citation statements)

References 79 publications

(55 reference statements)

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“…This could mean that the net effect in acromegaly reflects the balance between the direct and indirect insulin-antagonizing actions of GH and the insulin-sensitizing actions of IGF-I. This is in concordance with the observation that a low IGF-1/GH ratio is associated with abnormal glucose tolerance in acromegaly [13]. However, in clinical studies of patients with acromegaly, a stronger association has been demonstrated between insulin resistance and IGF-1 levels than with GH levels [14][15][16].…”

Section: Introductionsupporting

confidence: 80%

“…Some have found that both GH and IGF-1 correlate with insulin resistance evaluated by the homeostasis model assessment (HOMA) and area under curve for insulin [11], while others have concluded with a stronger association between levels of IGF-1 and insulin resistance than between levels of GH and insulin resistance [14][15][16]. On the other hand, IGF-1 has been suggested to have insulinsensitizing effects [12], and low IGF-1/GH ratio in subjects with acromegaly has been suggested indicative of abnormal glucose tolerance [13]. Generally, the scientific evidence of disturbed carbohydrate metabolism in subjects with acromegaly is broad [8-11, 13, 14, 16, 37-40, 47].…”

Section: Discussionmentioning

confidence: 99%

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Preoperative octreotide therapy and surgery in acromegaly: associations between glucose homeostasis and treatment response

et al. 2015

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In acromegaly, high GH/IGF-1 levels associate with abnormal glucose metabolism. Somatostatin analogs (SSAs) reduce GH and IGF-1 but inhibit insulin secretion. We studied glucose homeostasis in de novo patients with acromegaly and changes in glucose metabolism after treatment with SSA and surgery. In this post hoc analysis from a randomized controlled trial, 55 de novo patients with acromegaly, not using antidiabetic medication, were included. Before surgery, 26 patients received SSAs for 6 months. HbA1c, fasting glucose, and oral glucose tolerance test were performed at baseline, after SSA pretreatment and at 3 months postoperative. Area under curve of glucose (AUC-G) was calculated. Glucose homeostasis was compared to baseline levels of GH and IGF-1, change after SSA pretreatment, and remission both after SSA pretreatment and 3 months postoperative. In de novo patients, IGF-1/GH levels did not associate with baseline glucose parameters. After SSA pretreatment, changes in GH/IGF-1 correlated positively to change in HbA1c levels (both p < 0.03). HbA1c, fasting glucose, and AUC-G increased significantly during SSA pretreatment in patients not achieving hormonal control (all p < 0.05) but did not change significantly in patients with normalized hormone levels. At 3 months postoperative, HbA1c, fasting glucose, and AUC-G were significantly reduced in both cured and not cured patients (all p < 0.05). To conclude, in de novo patients with acromegaly, disease activity did not correlate with glucose homeostasis. Surgical treatment of acromegaly improved glucose metabolism in both cured and not cured patients, while SSA pretreatment led to deterioration in glucose homeostasis in patients not achieving biochemical control.

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Section: Introductionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Preoperative octreotide therapy and surgery in acromegaly: associations between glucose homeostasis and treatment response

et al. 2015

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“…Kasayama et al A few studies have addressed the issue of b-cell function in acromegaly. Among them, Kasayama et al (7) failed to demonstrate a correlation between b-cell function and GH or IGF1 levels, whereas Fukuoka et al (8) detected a weak correlation between IGI and IGF1 levels. Long-standing IR appears to cause b-cell 'exhaustion', which leads to impaired b-cell function and the development of type 2 DM in non-acromegalic subjects (17,18).…”

Section: Discussionmentioning

confidence: 99%

“…Studies have investigated impaired glucose metabolism in acromegaly, but it is unclear which clinical parameters (e.g. GH, IGF1) play a role in IR and/or impaired b-cell function in the disease (7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Impaired glucose metabolism in Japanese patients with acromegaly is restored after successful pituitary surgery if pancreatic β-cell function is preserved

Kinoshita

Fujii

Takeshita³

et al. 2011

European Journal of Endocrinology

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Objective: Impaired glucose metabolism is common in acromegaly, but it is not clear how glucose metabolism is impaired or what predicts its restoration after cure of the disease. To identify factors involved in the impairment of glucose metabolism in acromegaly, we evaluated clinical parameters before and immediately after surgical cure of the disease. Design and methods: We retrospectively analyzed clinical data of 92 consecutive Japanese patients with acromegaly who underwent successful pituitary surgery. Patients who had received medical therapy for acromegaly or insulin treatment for diabetes were excluded. We evaluated insulin resistance (IR) and pancreatic b-cell function in addition to GH and IGF1 levels before and after surgery. Results: In this study of Japanese patients with acromegaly, average body mass index (BMI) was 23.4, and no patient had a BMIO30. IR was involved in the impairment of glucose metabolism, which was restored upon surgical cure of acromegaly if b-cell function was preserved. Insufficient b-cell function did not improve after normalization of GH/IGF1 and was associated with impaired glucose metabolism before and after surgery. Results of receiver operating characteristic analysis of preoperative clinical parameters suggest that insulinogenic index (IGI) O0.50 best predicts restoration of normal glucose metabolism upon cure of acromegaly in Japanese patients. Conclusions: IR impairs glucose metabolism in acromegaly. Once b-cell function is impaired, abnormal glucose metabolism persists even after cure of acromegaly. IGIO0.50 indicates that b-cell function is preserved in non-obese Japanese patients with acromegaly.

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“…IGF-1 % ULN/GH reflects ratio of baseline IGF-1 % ULN and baseline GH levels. IGF-1 % ULN/GH is the value defined as the ratio of baseline IGF-1 % ULN level according to baseline GH level and this ratio is revised from previous literature data [25].…”

Section: Methodsmentioning

confidence: 99%

Impact of Glucose Metabolism Disorders on IGF-1 Levels in Patients with Acromegaly

et al. 2018

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In this study, we aimed to evaluate the presence of glucose metabolism abnormalities and their impact on IGF-1 levels in patients with acromegaly. Ninety-three patients with acromegaly (n=93; 52 males/41 females) were included in this study. Patients were separated into three groups such as; normal glucose tolerance (n=23, 25%), prediabetes (n=38, 41%), and diabetes mellitus (n=32, 34%). Insulin resistance was calculated with homeostasis model assessment (HOMA). HOMA-IR > 2.5 or ≤2.5 were defined as insulin resistant or noninsulin resistant groups, respectively. Groups were compared in terms of factors that may be associated with glucose metabolism abnormalities. IGF-1% ULN (upper limit of normal)/GH ratios were used to evaluate the impact of glucose metabolism abnormalities on IGF-1 levels. Patients with diabetes mellitus were significantly older with an increased frequency of hypertension (p<0.001, p=0.01, respectively). IGF-1% ULN/GH ratio was significantly lower in prediabetes group than in normal glucose tolerance group (p=0.04). Similarly IGF-1% ULN/GH ratio was significantly lower in insulin resistant group than in noninsulin resistant group (p=0.04). Baseline and suppressed GH levels were significantly higher in insulin resistant group than in noninsulin resistant group (p=0.024, p<0.001, respectively). IGF-1% ULN/GH ratio is a useful marker indicating glucose metabolism disorders and IGF-1 levels might be inappropriately lower in acromegalic patients with insulin resistance or prediabetes. We suggest that IGF-1 levels should be re-evaluated after the improvement of insulin resistance or glycemic regulation for the successful management of patients with acromegaly.

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Low Serum IGF-I/GH Ratio Is Associated with Abnormal Glucose Tolerance in Acromegaly

Cited by 10 publications

References 79 publications

Preoperative octreotide therapy and surgery in acromegaly: associations between glucose homeostasis and treatment response

Preoperative octreotide therapy and surgery in acromegaly: associations between glucose homeostasis and treatment response

Impaired glucose metabolism in Japanese patients with acromegaly is restored after successful pituitary surgery if pancreatic β-cell function is preserved

Impact of Glucose Metabolism Disorders on IGF-1 Levels in Patients with Acromegaly

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