Growth hormone, insulinlike growth factor-1, and insulinlike growth factor binding proteins 1 and 3 in chronic liver disease

Donaghy, Anthony J.; Ross, R. J. M.; Gimson, Alexander; Hughes, S. C. Cwyfan; Holly, Jeffrey M P; Williams, Roger

doi:10.1002/hep.1840210313

Cited by 93 publications

(87 citation statements)

References 42 publications

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“…28,29 Nevertheless, to our knowledge, no published study has evaluated serum IGF-I levels in the osteoporosis associated with chronic liver disease. Like others, [30][31][32] we found low serum IGF-I levels, which were related to the severity of the liver disease. In our study, BMD in LS was positively correlated with serum IGF-I levels, and patients with osteoporosis had serum IGF-I concentrations lower than patients without osteoporosis.…”

Section: Discussionsupporting

confidence: 86%

Bone mineral density, serum insulin-like growth factor I, and bone turnover markers in viral cirrhosis

et al. 1998

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Previous studies suggest that low bone mass is a complication of alcoholic liver disease. Nevertheless, little is known about bone mass and bone metabolism in viral cirrhosis. To evaluate the prevalence and magnitude of hepatic osteopenia in these patients, bone remodeling status, and its relationship with the severity of liver disease and serum levels of insulin-like growth factor I (IGF-I), we studied 32 consecutive patients with viral cirrhosis and no history of alcohol intake. Bone mineral density (BMD) was measured by dual x-ray absorptiometry in the lumbar spine (LS) and femoral neck (FN), and the values were expressed as the z score. Bone metabolism markers and hormone profiles were measured. Patients with viral cirrhosis showed reduced BMD in all sites (LS: ؊1.27 ؎ 1.06, P F .001; FN: ؊0.48 ؎ 0.96; P F .01). Of the 32 patients, 53% met the diagnostic criteria for osteoporosis. In patients, urine deoxypyridinoline (D-Pyr) as a marker of bone resorption and serum bone alkaline phosphatase (b-AP) as a marker of bone formation were significantly higher than in control subjects (P F .001 and P F .01, respectively). Serum IGF-I was lower than in control subjects (P F .001), and significant differences were also found between patients with and without osteoporosis (P F .05). BMD in LS correlated with severity of the disease, with serum levels of IGF-I, and with urine D-Pyr. Our findings show that viral cirrhosis is a major cause of osteoporosis in men, and that low serum IGF-I levels seem to play a role in the bone mass loss in these patients. The biochemical markers of bone remodeling suggest high-turnover osteoporosis in patients with viral cirrhosis. (HEPATOLOGY 1998;28:695-699.)

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Section: Discussionsupporting

confidence: 86%

Bone mineral density, serum insulin-like growth factor I, and bone turnover markers in viral cirrhosis

et al. 1998

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“…Furthermore, patients with severe hepatic cirrhosis have demonstrated high fasting levels of IGFBP-1 that are accompanied by elevated insulin levels. Interestingly, these patients had a less pronounced insulin-mediated suppression of IGFBP-1 during an oral glucose tolerance test (35). A similar pattern has been described in patients with AMI and abnormal glucose tolerance among whom the suppression of IGFBP-1 was significantly decreased during an oral glucose tolerance test, a finding that has been interpreted as increased hepatic insulin resistance (20).…”

Section: Baseline Characteristicssupporting

confidence: 55%

IGF Binding Protein 1 Predicts Cardiovascular Morbidity and Mortality in Patients With Acute Myocardial Infarction and Type 2 Diabetes

et al. 2007

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OBJECTIVE -There are indications that the IGF system is related to both type 2 diabetes and cardiovascular disease (CVD). We tested the hypothesis that low IGF-I and high IGFbinding protein (IGFBP)-1 predict future cardiovascular mortality and morbidity in patients with acute myocardial infarction (AMI) and type 2 diabetes. RESEARCH DESIGN AND METHODS -The Diabetes MellitusInsulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 Trial recruited 1,253 patients with type 2 diabetes and AMI, of whom 575 were enrolled in a biochemical program with repeated blood sampling. Primary and secondary end points included adjudicated cardiovascular mortality and a composite of cardiovascular events (cardiovascular death, reinfarction, or stroke). Multiple Cox proportional hazard regression was used to study the relationship between the end points and the variables. Admission variables were used for the survival analysis and for blood glucose, and A1C updated mean values during follow-up were also available. CONCLUSIONS -High levels of IGFBP-1 at admission are associated with increased risk for cardiovascular mortality and morbidity in type 2 diabetes patients with AMI. RESULTS Diabetes Care 30:2343-2348, 2007P atients with type 2 diabetes have an increased risk for cardiovascular disease (CVD) (1). The prognosis after an acute myocardial infarction (AMI) does, indeed, already deteriorate at glucose levels in the upper normal range (2,3). The importance is underlined by the high prevalence of AMI patients with previously undetected glucose abnormalities (4 -6). The increased cardiovascular risk cannot be completely explained by traditional risk factors, and mechanisms amplifying their impact are not fully understood (7). Thus, the search for novel risk factors linking type 2 diabetes and CVD is important (8).The IGF-I system has been related to poor glucose control, and low levels of IGF-I have been related to future type 2 diabetes (9). In addition, the IGF-I system and especially low IGF-I, low IGF binding protein (IGFBP)-1, and high IGFBP-3 relate to increased cardiovascular risk (10,11). Thus, it is of interest to explore the IGF-I system as a potential novel risk factor and as a possible link between type 2 diabetes and subsequent cardiovascular complications (12). The hepatic production of IGFBP-1 is downregulated by insulin (13). Accordingly, in the general population, there is a correlation between low levels of IGFBP-1 and hyperinsulinemia, and these findings may link to an increased cardiovascular risk (14,15). However, IGFBP-1 concentrations rise during the development of type 2 diabetes, despite persisting hyperinsulinemia, indicating increased hepatic insulin resistance during disease progression (16,17). These observations were supported by van den Berghe et al. (18), who demonstrated that patients admitted to the intensive care unit with elevated levels of IGFBP-1 presented a poor prognosis regarding mortality, a finding that related to acute hepatic insulin resistance. Furthermore, there is a correla...

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“…GH could also regulate immunity and metabolism [6] . Furthermore, liver is the main target organ of GH in vivo, and the center of GH-IGF axis [7,8] . It has been found that decreased serum IGF-1, IGFBP3 and ALS had a close relation to liver reserve function and the prognoses of liver cirrhosis patients [9] .…”

Section: Discussionmentioning

confidence: 99%

Combined human growth hormone and lactulose for prevention and treatment of multiple organ dysfunction in patients with severe chronic hepatitis B

Ding

Shan²,

Zhang³

et al. 2005

WJG

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AIM:To evaluate the efficiency and safety of combined recombinant human growth hormone (rhGH) and lactulose for treatment and/or prevention of multiple organ dysfunction in patients with chronic severe hepatitis B. METHODS:Forty-eight inpatients with chronic severe hepatitis B were randomly divided into rhGH group (n = 28) and control group (n = 20). In rhGH group, 4-4.5 IU of rhGH was injected intramuscularly once daily for 2-4 wk, and 100 mL of enema containing 30 mL of lactulose, 2 g of metronidazole and 0.9% saline was administered every 2 d for 2-4 wk. Their symptoms and complications were noted. Liver and kidney functions were analyzed by an Olympus analyzer. Serum GH, IGF-1, IGFBP1 and IGFBP3 were measured by ELISA. RESULTS:Clinical symptoms of 90% of these patients in rhGH group were obviously improved. The total effectiveness in rhGH group was better than that in control group (75% vs 40%, P<0.05). After 2-and 4-wk treatment of rhGH respectively, serum albumin (26.1±4.1 vs 30.2±5.3, 31.9±5.1 g/L), prealbumin (79.6±28.0 vs 106.6±54.4, 108.4±55.0 g/L), cholesterol (76.3±16.7 vs 85.6±32.3, 96.1±38.7 mg/dL), and IGFBP1 (56.8±47.2 vs 89.7±50.3 ng/mL after 2 wk) were significantly increased compared to control group (P<0.05). However, serum GH was decreased. The increase of serum IGF1 and IGFBP3 after rhGH treatment was also observed.CONCLUSION: rhGH in combination with lactulose may be beneficial to the prevention and treatment of multiple organ dysfunction in patients with chronic severe hepatitis.

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Growth hormone, insulinlike growth factor-1, and insulinlike growth factor binding proteins 1 and 3 in chronic liver disease

Cited by 93 publications

References 42 publications

Bone mineral density, serum insulin-like growth factor I, and bone turnover markers in viral cirrhosis

Bone mineral density, serum insulin-like growth factor I, and bone turnover markers in viral cirrhosis

IGF Binding Protein 1 Predicts Cardiovascular Morbidity and Mortality in Patients With Acute Myocardial Infarction and Type 2 Diabetes

Combined human growth hormone and lactulose for prevention and treatment of multiple organ dysfunction in patients with severe chronic hepatitis B

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