Low levels of insulin-like growth-factor-binding protein-1 (IGFBP-1) are prospectively associated with the incidence of type 2 diabetes and impaired glucose tolerance (IGT): The Söderåkra Cardiovascular Risk Factor Study

Petersson, Ulla; Östgren, Carl Johan; Brudin, Lars; Brismar, Kerstin; Nilsson, Peter M.

doi:10.1016/j.diabet.2008.11.003

Cited by 64 publications

(59 citation statements)

References 33 publications

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“…Fasting IGFBP-1 is a good predictive marker of abnormal glucose homeostasis, with low values predicting the development of impaired fasting glucose, impaired glucose tolerance and type 2 diabetes 8–17 years later [16,17,69,70]. In women who go on develop diabetes 8 years later, IGFBP-1 concentrations are low relative to insulin levels, perhaps due to a novel inhibitor of IGFBP-1.…”

Section: Impaired Glucose Tolerance and Type 2 Diabetesmentioning

confidence: 99%

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The Insulin-Like Growth Factor System in Obesity, Insulin Resistance and Type 2 Diabetes Mellitus

Lewitt

Dent

Hall

2014

JCM

115

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The insulin-like growth factor (IGF) system, acting in concert with other hormone axes, is important in normal metabolism. In obesity, the hyperinsulinaemia that accompanies peripheral insulin resistance leads to reduced growth hormone (GH) secretion, while total IGF-I levels are relatively unchanged due to increased hepatic GH sensitivity. IGF-binding protein (IGFBP)-1 levels are suppressed in relation to the increase in insulin levels in obesity and low levels predict the development of type 2 diabetes several years later. Visceral adiposity and hepatic steatosis, along with a chronic inflammation, contribute to the IGF system phenotype in individuals with metabolic syndrome and type 2 diabetes mellitus, including changes in the normal inverse relationship between IGFBP-1 and insulin, with IGFBP-1 concentrations that are inappropriately normal or elevated. The IGF system is implicated in the vascular and other complications of these disorders and is therefore a potential therapeutic target.

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Section: Impaired Glucose Tolerance and Type 2 Diabetesmentioning

confidence: 99%

“…Low IGF-I concentrations have been shown to predict later glucose intolerance and type 2 diabetes in some studies [72] and not others [16,17,69]. Free IGF-I concentrations are associated with incident diabetes in women with insulin levels above, and IGFBP-1 levels below, the median [70].…”

Section: Impaired Glucose Tolerance and Type 2 Diabetesmentioning

confidence: 99%

The Insulin-Like Growth Factor System in Obesity, Insulin Resistance and Type 2 Diabetes Mellitus

Lewitt

Dent

Hall

2014

JCM

115

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“…Low levels of circulating insulin-like growth factor binding protein-1 (IGFBP1) is associated with insulin resistance and Type 2 diabetes [55], and is also a predictor for development of Type 2 diabetes [56]. To investigate how this gene is regulated, Gu et al analyzed IGFBP1 DNA methylation in blood from patients with Type 2 diabetes and age-matched controls [38].…”

Section: Epigenetic Alterations and Insulin Sensitivitymentioning

confidence: 99%

DNA Methylation as a Diagnostic and Therapeutic Target in the Battle Against Type 2 Diabetes

Rönn

Ling

2015

Epigenomics

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Type 2 diabetes (T2D) develops due to insulin resistance and impaired insulin secretion, predominantly in genetically predisposed subjects exposed to nongenetic risk factors like obesity, physical inactivity and ageing. Emerging data suggest that epigenetics also play a key role in the pathogenesis of T2D. Genome-wide studies have identified altered DNA methylation patterns in pancreatic islets, skeletal muscle and adipose tissue from subjects with T2D compared with nondiabetic controls. Environmental factors known to affect T2D, including obesity, exercise and diet, have also been found to alter the human epigenome. Additionally, ageing and the intrauterine environment are associated with differential DNA methylation. Together, these data highlight a key role for epigenetics and particularly DNA methylation in the growing incidence of T2D.

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“…We showed that compared with the low-dose therapy, high-dose atorvastatin was associated with lowering of IGFBP1 levels, which has been associated with an increased risk for gestational diabetes, glucose tolerance and type 2 diabetes (4,10,11,22). The cause of the dose-dependent effect of atorvastatin on IGFBP1 concentration is unclear.…”

Section: Differential Effects Of Statin Dose On Igfbp1 and Implicatiomentioning

confidence: 88%

“…IGF binding protein 1 (IGFBP1) is an acute modulator of IGF1 and IGF2 bioavailability, and altered IGFBP1 levels have also been linked to diabetes rates (10,11,12). IGFBP3 is the principal carrier protein of IGF1 and IGF2.…”

Section: Introductionmentioning

confidence: 99%

Atorvastatin administration is associated with dose-related changes in IGF bioavailability

Narayanan

Gittins

Siddals

et al. 2013

European Journal of Endocrinology

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Objective: IGF levels, their binding proteins (IGFBPs) and high-dose statin therapy have been linked to the development of diabetes. We aimed to identify whether atorvastatin caused dose-related changes in IGF proteins. Design and methods: We measured IGF1, IGF2, IGFBP1 and IGFBP3 concentrations at baseline, 6 and 12 months in Protection Against Nephropathy in Diabetes with Atorvastatin trial participants with type 2 diabetes randomised to 10 mg (nZ59) vs 80 mg (nZ60) of atorvastatin (nZ119; mean (S.D.): age 64 (10) years; 83% male; HbA1c 61 (10) mmol/mol; blood pressure 131/73 mmHg). Results: Atorvastatin was associated with overall reductions in circulating IGF1, IGF2 and IGFBP3 concentrations (P!0.05 for all changes). The adjusted mean (95% CI) between-group differences that indicate dose-related changes in IGF proteins were not significant for IGF1: K3 (K21 to 14) ng/ml; IGF2: K23 (K65 to 18) ng/ml and IGFBP3: K0.34 (K0.71 to 0.03) mg/ml, negative values indicating numerically greater lowering with high dose. The IGFBP1 concentration did not change with atorvastatin therapy overall but the adjusted mean (95% CI) between-group difference indicating a dose-related change in log IGFBP1 was highly significant K0.41 (K0.69 to 0.13, PZ0.004). Conclusion: IGF1, IGF2 and IGFBP3 concentrations decreased following atorvastatin therapy. A differential effect of low-vs high-dose atorvastatin on IGFBP1 concentrations was observed with likely implications for IGF bioavailability. The dose-related differential impact of atorvastatin treatment on concentration of IGF proteins merits investigation as a mechanism to explain the worsening of glucose tolerance with statin therapy.

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Low levels of insulin-like growth-factor-binding protein-1 (IGFBP-1) are prospectively associated with the incidence of type 2 diabetes and impaired glucose tolerance (IGT): The Söderåkra Cardiovascular Risk Factor Study

Cited by 64 publications

References 33 publications

The Insulin-Like Growth Factor System in Obesity, Insulin Resistance and Type 2 Diabetes Mellitus

The Insulin-Like Growth Factor System in Obesity, Insulin Resistance and Type 2 Diabetes Mellitus

DNA Methylation as a Diagnostic and Therapeutic Target in the Battle Against Type 2 Diabetes

Atorvastatin administration is associated with dose-related changes in IGF bioavailability

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