Circulating concentrations of insulin-like growth factor-I and development of glucose intolerance: a prospective observational study

Sandhu, Manjinder S.; Heald, Adrian; Gibson, John M.; Cruickshank, J.K.; Dunger, David B.; Wareham, Nicholas J.

doi:10.1016/s0140-6736(02)08655-5

Cited by 445 publications

(442 citation statements)

References 26 publications

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“…Elevated BMI was associated with both higher IGF-I and higher IGFBP-3. IGF-I was negatively associated with fasting and 2-h glucose, suggesting a direct link between lower circulating IGF-I and dysregulation of post-prandial glucose, as previously reported in a prospective cohort study [6]. Increasing IGFBP-3 was related to both higher IGF-I and higher fasting insulin, in keeping with the in vitro finding that IGF-I and insulin increase the abundance of IGFBP-3 mRNA in hepatocytes [28].…”

Section: Relationship Of Igfbp-1 To Established Cardiovascular Risk Fsupporting

confidence: 88%

“…We and others have established close links between the IGF system and the development of impaired glucose tolerance, obesity and macrovascular disease [15][16][17][18]. In a white European population, we demonstrated that such changes predict the development of worsening glucose tolerance at the 5-year follow-up [6]. Recently, higher circulating IGF-I levels and a high IGF-I : IGFBP-3 ratio have been associated with the development of breast cancer in premenopausal women [19] and prostate cancer in men [20].…”

Section: Introductionsupporting

confidence: 55%

“…There is accumulating evidence that the IGF system is closely involved in the progression to impaired glucose tolerance [6], with the combination of low circulating IGF-I and low IGF binding protein (IGFBP)-1 at baseline predisposing to impaired glucose handling at the 5-year follow-up. The IGF system has been implicated in the pathogenesis of hypertension [7], atheromatous vascular disease [8,9], cardiomegaly [10], ischaemic disease [11] and cardiac failure [12,13].…”

Section: Introductionmentioning

confidence: 99%

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Marked differences in the IGF system that are associated with migration in comparable populations of Gujaratis living in Sandwell, UK, and Gujarat, India

et al. 2005

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Aims/hypotheses: We previously reported independent links between the IGF system and the development of impaired glucose tolerance and cardiovascular risk. This study tests the hypothesis that the lifestyle change which accompanies population migration, with attendant increases in cardiovascular risk, is reflected by changes in the IGF system. Materials and methods: We compared a specific Gujarati community in Sandwell, UK (n=205), with people still resident in the same villages of origin near Navsari, India (n=246). We performed anthropometry and measured fasting plasma insulin, IGF-I, insulin-like growth factor binding protein (IGFBP)-1 and IGFBP-3. Results: Daily calorie intake, BMI and WHR were significantly higher in UK Gujaratis than in Indian Gujaratis. IGFBP-1 was significantly lower in UK migrants (mean 29.5 [95% CI 25.9-33.0] vs 56.5 [50.6-62.5]μg/l; F=48.4, p<0.001). Conversely, fasting insulin, IGFBP-3 and IGF-I were all higher in UK Gujaratis (mean IGF-I 145.9 [138.1-153.6]ng/ml in UK Gujaratis and 100.9 [94.6-107.3] ng/ml in Navsari Gujaratis; F=76.6, p<0.001). These differences were still apparent when adjustment was made for BMI by location for IGF-I (F=57.4, p<0.001) and IGFBP-3 (F=5.7, p=0.02), but were no longer apparent for IGFBP-1 and insulin. At the population level, the decrease in IGFBP-1 for a given increase in insulin was significantly smaller in UK Gujaratis, suggesting greater hepatic insulin resistance in this group. Conclusions/interpretation: Environmental factors have profound effects on circulating IGF system components and on the relationship between IGFBP-1, IGF-I and related metabolic variables. This may have long-term implications for the development of worsening glucose tolerance and cardiovascular disease.

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Section: Relationship Of Igfbp-1 To Established Cardiovascular Risk Fsupporting

confidence: 88%

Section: Introductionsupporting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

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Marked differences in the IGF system that are associated with migration in comparable populations of Gujaratis living in Sandwell, UK, and Gujarat, India

et al. 2005

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“…Paradoxically, low IGF‐1 levels are associated with increased risk for numerous diseases of aging in humans, including cardiovascular disease (CVD) (Juul et al ., 2002), type 2 diabetes (T2DM) (Sandhu et al ., 2002), and frailty (Leng et al ., 2004). Moreover, it was recently shown that long‐lived daf‐2 mutants spent a larger proportion of life in a frail state than wild‐type Caenorhabditis elegans (Bansal et al ., 2015).…”

Section: Introductionmentioning

confidence: 99%

Central insulin‐like growth factor‐1 ( IGF ‐1) restores whole‐body insulin action in a model of age‐related insulin resistance and IGF ‐1 decline

et al. 2015

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SummaryLow insulin‐like growth factor‐1 (IGF‐1) signaling is associated with improved longevity, but is paradoxically linked with several age‐related diseases in humans. Insulin‐like growth factor‐1 has proven to be particularly beneficial to the brain, where it confers protection against features of neuronal and cognitive decline. While aging is characterized by central insulin resistance in the face of hyperinsulinemia, the somatotropic axis markedly declines in older humans. Thus, we hypothesized that increasing IGF‐1 in the brain may prove to be a novel therapeutic alternative to overcome central insulin resistance and restore whole‐body insulin action in aging. Utilizing hyperinsulinemic‐euglycemic clamps, we show that old insulin‐resistant rats with age‐related declines in IGF‐1 level demonstrate markedly improved whole‐body insulin action, when treated with central IGF‐1, as compared to central vehicle or insulin (P < 0.05). Furthermore, central IGF‐1, but not insulin, suppressed hepatic glucose production and increased glucose disposal rates in aging rats (P < 0.05). Taken together, IGF‐1 action in the brain and periphery provides a ‘balance’ between its beneficial and detrimental actions. Therefore, we propose that strategies aimed at ‘tipping the balance’ of IGF‐1 action centrally are the optimal approach to achieve healthy aging and longevity in humans.

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“…1,2 On the other hand, higher plasma concentrations of IGF-I have been found to be associated with a reduced risk of osteoporosis, 3 diabetes 4 and possibly heart disease. 5 Insulin-like growth factor-I, together with insulin, is central to the regulation of anabolic (growth) processes as a function of available energy and essential nutrients (e.g.…”

Section: Introductionmentioning

confidence: 99%

Body mass index, waist circumference and waist–hip ratio and serum levels of IGF-I and IGFBP-3 in European women

et al. 2006

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Objective: To examine the relationship between body mass index (BMI) and waist-hip ratio (WHR) with serum levels of insulinlike growth factor-I (IGF-I), and its binding protein (IGFBP)-3. Design: Cross-sectional study on 2139 women participating in a case-control study on breast cancer and endogenous hormones. Data on lifestyle and reproductive factors were collected by means of questionnaires. Body height, weight, waist and hip circumferences were measured. Serum levels of IGF-I and insulin-like binding protein (IGFBP)-3 were measured by enzymelinked immunosorbent assays. Adjusted mean levels of IGF-I and IGFBP-3 across quintiles of BMI, waist circumference, and WHR were calculated by linear regression. Results were adjusted for potential confounders associated with IGF-I and IGFBP-3. Results: Adjusted mean serum IGF-I values were lower in women with BMIo22.5 kg/m 2 or BMI429.2 kg/m 2 compared to women with BMI within this range (P heterogeneity o0.0001, P trend ¼ 0.35). Insulin-like growth factor-I was not related to WHR after adjustment for BMI. IGF-binding protein-3 was linearly positively related to waist and WHR after mutual adjustment. The molar ratio IGF-I/IGFBP-3 had a non-linear relation with BMI and a linear inverse relationship with WHR (P trend ¼ 0.005). Conclusions: Our data confirm the nonlinear relationship of circulating IGF-I to total adiposity in women. Serum IGFBP-3 was positively related to central adiposity. These suggest that bioavailable IGF-I levels could be lower in obese compared to nonobese women and inversely related to central adiposity.

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Circulating concentrations of insulin-like growth factor-I and development of glucose intolerance: a prospective observational study

Cited by 445 publications

References 26 publications

Marked differences in the IGF system that are associated with migration in comparable populations of Gujaratis living in Sandwell, UK, and Gujarat, India

Marked differences in the IGF system that are associated with migration in comparable populations of Gujaratis living in Sandwell, UK, and Gujarat, India

Central insulin‐like growth factor‐1 ( IGF ‐1) restores whole‐body insulin action in a model of age‐related insulin resistance and IGF ‐1 decline

Body mass index, waist circumference and waist–hip ratio and serum levels of IGF-I and IGFBP-3 in European women

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