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J A Janssen

Publications and source records attributed to J A Janssen.

At least 19 recordsLinked to original sources
PubMed2001

[Growth hormone receptor antagonists: potential indications].

Pegvisomant is a mutated human growth hormone molecule, which binds to the growth hormone receptor. This binding, however, does not lead to signal transduction. Therefore, in high concentrations pegvisomant acts as a growth hormone receptor antagonist. In a short term study (3 months) pegvisomant was shown to be an effective treatment for acromegaly. On theoretical grounds decreasing the biological effects of growth hormone in patients with diabetes mellitus could have a favourable impact on the severity of the secondary complications associated with this disease. Animal models for diabetic retino- and nephropathy are in accordance with this concept. Human data are lacking but clinical studies investigating the effect of pegvisomant in diabetes mellitus are in preparation. Growth hormone, either directly or via its downstream effector insulin-like growth factor-I (IGF-I) has been implicated as an important factor in the growth of malignant tumours. Animal studies in which human colon and breast cancer models were used showed that pegvisomant can powerfully decrease tumour growth. Studies in cancer patients have not yet started.

Acromegaly↗
PubMed2001

Effects of fasting and pegvisomant on the GH-releasing hormone and GH-releasing peptide-6 stimulated growth hormone secretion.

OBJECTIVE: Pegvisomant is a mutated GH molecule which prevents functional dimerization and subsequent activation of the growth hormone receptor. Pegvisomant and fasting both lead to GH resistance. DESIGN AND PATIENTS: We performed a double-blind placebo-controlled cross-over study comparing the effects of pegvisomant and fasting on the GH-releasing hormone (GHRH)- and GH-releasing peptide-6 (GHRP-6)-stimulated GH-release before and after 3 days of fasting in 10 healthy lean male subjects. We also performed a single-arm open label study under nonfasting conditions in five of these subjects. On day 1, in random order, at 0800 h, a GHRP-6 or GHRH test was performed. At 1600 h, a GHRH (if the first test was a GHRP-6 test) or GHRP-6-test (if the first test was a GHRH test) was done. After the second test either pegvisomant (80 mg as a single subcutaneous injection) or placebo was administered. On day 4, GHRP-6 and GHRH tests were performed in the same order as on day 1. During the cross-over study, subjects fasted from 2400 h on day 1 until the end of the study. MEASUREMENTS: During the GH stimulation tests, blood samples were drawn every 15 min from 15 to 120 min. GH was determined in all samples. Total insulin-like growth factor (IGF)-I and free IGF-I were determined from the samples at 0 min only. RESULTS: Three days of fasting alone and pegvisomant alone as well as in combination increased GH concentrations, whereas a decrease in serum-free, but not total, IGF-I concentrations was observed. On day 4, fasting and pegvisomant, either alone or in combination, significantly increased GH concentrations after GHRH compared to baseline. Pegvisomant alone did not increase GH concentrations after GHRP-6 administration. Fasting alone increased GH levels after GHRP-6 administration. The combination of fasting and pegvisomant had a synergistic effect on GH release after GHRP-6. CONCLUSION: These human in vivo data suggest that: (1) circulating free IGF-I, and not total IGF-I, is the major component in the negative feedback on GH secretion; (2) increased pituitary GHRH receptor expression plays a role in the mechanism whereby fasting leads to increased GH concentrations; (3) in vivo, GHRP-6 sensitivity seems to be regulated primarily by metabolic factors and not by changes in GH-IGF-I axis.

Adult↗
PubMed2001

Acute effect of pegvisomant on cardiovascular risk markers in healthy men: implications for the pathogenesis of atherosclerosis in GH deficiency.

Cardiovascular risk is increased in GH deficiency (GHD). GHD adults are frequently abdominally obese and display features of the metabolic syndrome. Otherwise healthy abdominally obese subjects have low GH levels and show features of the metabolic syndrome as well. We investigated in healthy nonobese males the effect of the GH receptor antagonist pegvisomant in different metabolic conditions. This is a model for acute GHD without the alterations in body composition associated with GHD. We compared the effect of pegvisomant with that of placebo before and after 3 d of fasting. In addition, we investigated the effect of pegvisomant under normal, i.e. fed, conditions. Three days of fasting as well as pegvisomant alone decreased serum free IGF-I levels (1.0 +/- 0.15 vs. 0.31 +/- 0.05 ng/ml and 0.86 +/- 0.23 vs. 0.46 +/- 0.23 ng/ml, respectively). Fasting in combination with pegvisomant also decreased serum free IGF-I levels (1.0 +/- 0.15 vs. 0.31 +/- 0.07 ng/ml). Treatment with pegvisomant had no additional influence on the decline of free IGF-I induced by fasting. Pegvisomant alone had no influence on insulin sensitivity. The increase in insulin sensitivity induced by fasting was comparable to the increase in insulin sensitivity induced by fasting combined with pegvisomant. Among serum lipid concentrations, only serum triglycerides increased significantly as a result of pegvisomant alone (1.0 +/- 0.2 vs. 1.6 +/- 0.4 mmol/liter). The changes in lipid concentrations induced by fasting alone or pegvisomant were not different from those induced by pegvisomant alone. von Willebrand factor antigen levels declined significantly under the influence of pegvisomant alone (1.1 +/- 0.07 vs. 0.8 +/- 0.06 U/ml). In conclusion, in different metabolic conditions the GH receptor antagonist pegvisomant induces no significant acute changes in the major risk markers for cardiovascular disease. These data suggest that the secondary metabolic changes, e.g. abdominal obesity or inflammatory factors, that develop as a result of long-standing GHD are of primary importance in the pathogenesis of atherosclerosis in patients with GHD.

Adult↗
PubMed2001

Blockade of the growth hormone (GH) receptor unmasks rapid GH-releasing peptide-6-mediated tissue-specific insulin resistance.

The roles of GH and its receptor (GHR) in metabolic control are not yet fully understood. We studied the roles of GH and the GHR using the GHR antagonist pegvisomant for metabolic control of healthy nonobese men in fasting and nonfasting conditions. Ten healthy subjects were enrolled in a double blind, placebo-controlled study on the effects of pegvisomant on GHRH and GH-releasing peptide-6 (GHRP-6)-induced GH secretion before and after 3 days of fasting and under nonfasting conditions (n = 5). Under the condition of GHR blockade by pegvisomant in the nonfasting state, GHRP-6 (1 microg/kg) caused a increase in serum insulin (10.3 +/- 2.1 vs. 81.3 +/- 25.4 mU/L; P < 0.001) and glucose (4.2 +/- 0.3 vs. 6.0 +/- 0.6 mmol/L; P < 0.05) concentrations. In this group, a rapid decrease in serum free fatty acids levels was also observed. These changes were not observed under GHR blockade during fasting or in the absence of pegvisomant. We conclude that although these results were obtained from an acute study, and long-term administration of pegvisomant could render different results, blockade of the GHR in the nonfasting state induces tissue-specific changes in insulin sensitivity, resulting in an increase in glucose and insulin levels (indicating insulin resistance of liver/muscle), but probably also in an increase in lipogenesis (indicating normal insulin sensitivity of adipose tissue). These GHRP-6-mediated changes indicate that low GH bioactivity on the tissue level can induce changes in metabolic control, which are characterized by an increase in fat mass and a decrease in lean body mass. As a mechanism of these GHRP-6-mediated metabolic changes in the nonfasting state, direct nonpituitary-mediated GHRP-6 effects on the gastroentero-hepatic axis seem probable.

Adult↗
PubMed2001

Control of tumor size and disease activity during cotreatment with octreotide and the growth hormone receptor antagonist pegvisomant in an acromegalic patient.

We describe the case of an acromegalic subject, who was the first patient ever treated with the GH receptor antagonist pegvisomant. Furthermore, in this particular patient, progression in tumor size was encountered during treatment with pegvisomant. The patient described did benefit from cotreatment with pegvisomant and octreotide, including decreased GH levels, normalization of serum insulin-like growth factor I concentrations, and improvement of visual field defects.

Acromegaly↗
PubMed2001

Systemic ghrelin levels in subjects with growth hormone deficiency are not modified by one year of growth hormone replacement therapy.

OBJECTIVE: Ghrelin stimulates growth hormone (GH) secretion both in vivo and in vitro. Ghrelin is mainly produced in and released from the stomach but it is probably also produced in the hypothalamic arcuate nucleus. Whether pituitary GH release is under the control of ghrelin from the stomach and/or from the arcuate nucleus is not known. Moreover, no data on the feedback of GH on systemic ghrelin concentrations are available. It has recently been suggested that ghrelin may induce obesity. DESIGN: In this study, we addressed the following two questions: a) are circulating ghrelin levels increased in human GH deficiency (GHD), and b) does GH treatment modify ghrelin levels in human GHD? METHODS: The study group consisted of 23 patients with GHD. Eighteen had developed adult-onset GHD and five had developed GHD in their childhood (childhood-onset GHD). Ghrelin was measured with a commercially available radioimmunoassay. All measurements were performed twice, first at baseline, before the start of GH replacement therapy, and then again after one year of therapy. GH doses were adjusted every 3 months, targeting serum total IGF-I levels within the normal gender- and age-related reference values for the healthy population. Maintenance doses were continued once the target serum total IGF-I levels were reached. RESULTS: The sum of skinfolds and body water increased significantly, body fat mass and percentage body fat decreased significantly and body mass index and waist-hip ratio were not significantly changed by one year of GH replacement therapy. Before the start of GH replacement therapy, mean value and range for fasting ghrelin in the studied GHD subjects tended to be lower in comparison with healthy subjects in the control group although the difference did not reach significance (GHD ghrelin mean 67.8 pmol/l, range 37.6-116.3 pmol/l; control mean 83.8 pmol/l, range 35.4-132 pmol/l; P=0.11). One year of GH replacement therapy did not modify circulating ghrelin levels (ghrelin before GH therapy: 67.8 pmol/l, range 37.6-116.3 pmol/l; after GH therapy: 65.3 pmol/l, range 35.8-112.6; P=0.56). CONCLUSIONS: We did not observe elevated ghrelin levels in adult GHD subjects and GH replacement therapy did not modify circulating ghrelin levels, despite significant decreases in body fat mass and percentage body fat. It is conceivable that the lack of ghrelin modifications after long-term GH therapy was due to the reduction of adiposity and insulin on one hand, and increased GH secretion on the other. However, it is still possible that systemic ghrelin is involved in the development of obesity, both in normal and GHD subjects.

Adipose Tissue↗
PubMed2001

A polymorphism in the gene for IGF-I: functional properties and risk for type 2 diabetes and myocardial infarction.

Evidence is accumulating that low levels of IGF-I play a role in the pathogenesis of type 2 diabetes and cardiovascular diseases. We examined the role of a genetic polymorphism in the promoter region of the IGF-I gene in relation to circulating IGF-I levels and growth measured as body height, and we studied the relationship of this polymorphism with type 2 diabetes and myocardial infarction. The relation between the IGF-I polymorphism and body height was assessed in a population-based sample of 900 subjects from the Rotterdam Study. Within each genotype stratum, 50 subjects were randomly selected for a study of the relation of this polymorphism with serum IGF-I levels. To assess the risk for type 2 diabetes, we studied 220 patients and 596 normoglycemic control subjects. For myocardial infarction, 477 patients with evidence of myocardial infarction on electrocardiogram and 808 control subjects were studied. A 192-bp allele was present in 88% of the population, suggesting that this is the wild-type allele from which all other alleles originated. Body height was, on average, 2.7 cm lower (95% CI for difference -4.6 to -0.8 cm, P = 0.004), and serum IGF-I concentrations were 18% lower (95% CI for difference -6.0 to -1.3 mmol/l, P = 0.003) in subjects who did not carry the 192-bp allele. In noncarriers of the 192-bp allele, an increased relative risk for type 2 diabetes (1.7 [95% CI 1.1-2.7]) and for myocardial infarction (1.7 [95% CI 1.1-2.5]) was found. In patients with type 2 diabetes, the relative risk for myocardial infarction in subjects without the 192-bp allele was 3.4 (95% CI 1.1-11.3). Our study suggests that a genetically determined exposure to relatively low IGF-I levels is associated with an increased risk for type 2 diabetes and myocardial infarction.

Aged↗
PubMed2000

[Current role of metformin in treatment of diabetes mellitus type 2].

Metformin-associated lactic acidosis is not necessarily due to metformin accumulation. It appears that mortality in patients receiving metformin who develop lactic acidosis is mostly linked to underlying disease. It has been suggested that metformin should be the first-line agent for the treatment of obese type 2 diabetic patients since metformin was associated with a significant decrease in macrovascular events and a reduction of all-cause mortality in the United Kingdom Prospective Diabetes Study (UKPDS) in a substudy. However, in this substudy no significant decrease in microvascular complications was observed in obese subjects with intensive metformin therapy. In addition, the use of metformin in combination with sulfonylurea seemed to be associated with excess risk of diabetes-related and all-cause mortality in obese subjects. Due to the discrepant and contradictory nature of the results in the obese patients and a lack of power the UKPDS offered no decision for any drug for initial therapy of type 2 diabetes. The main message of the UKPDS is that lowering of the blood glucose to the normal range is beneficial irrespective of the hypoglycaemic agent used. A rational approach to therapy in a type 2 diabetes patient who fails to sufficiently lower blood sugar with diet and weight loss is to begin therapy with a sulfonylurea or metformin and to add another oral agent if the desired glycaemic control is not achieved.

Acidosis, Lactic↗
PubMed2000

Circulating IGF-I and its protective role in the pathogenesis of diabetic angiopathy.

Poor glycaemic control in type 1 diabetes is associated with elevated serum IGFBP-1 levels and reduced rather than elevated serum IGF-I levels. Increasing age is accompanied by a further decrease in serum IGF-I levels as well as an increase in IGFBP-l levels in adult diabetic type 1 and type 2 subjects. This is especially observed in diabetic type 1 subjects with manifest microvascular complications. IGFBP-I has been proposed as one of the IGF-I inhibitors in the serum of diabetics. Lowered IGF-I and increased IGFBP-1 levels in the blood may thus result in decreased IGF-I bioavailability at the tissue level. We hypothesize that the premature and progressive decline in serum IGF-I bioactivity during ageing in diabetics ultimately results in insufficient protective effects by IGF-I in the kidneys, eyes and neurones, and thus the progression of diabetic microvascular complications. If this hypothesis is proven to be right, treatment of diabetic patients with IGF-I (eventually complexed to IGFBPs) as an adjunct to insulin might prevent and not worsen the development of diabetic microvascular complications.

Adolescent↗
PubMed2000

A prospective study on circulating insulin-like growth factor I (IGF-I), IGF-binding proteins, and cognitive function in the elderly.

The objective of this study was to investigate the longitudinal relation between the insulin-like growth factor I (IGF-I)/IGF-binding protein (IGFBP) system and cognitive function. The study population consisted of a sample of 186 healthy participants from the population-based Rotterdam Study, aged 55-80 yr. At baseline, we determined fasting blood levels of free and total IGF-I, IGFBP-1, and IGFBP-3. The 30-point Mini-Mental State Examination (MMSE) was used to assess cognitive impairment at baseline (MMSE score of <26; 6% of the sample) and cognitive decline after, on the average, 1.9 yr of follow-up (drop in MMSE score of >1 point/year; 22% of the sample). Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using logistic regression, with adjustment for age, sex, education, body mass index, and fasting insulin levels. Total IGF-I appeared to be inversely related to cognitive impairment, although not significantly. Higher total IGF-I and the total IGF-I/IGFBP-3 ratio were associated with less cognitive decline (OR per SD increase = 0.65; 95% CI = 0.44-0.95 and OR = 0.59; 95% CI = 0.39-0.87, respectively). No relation was observed between free IGF-I and cognitive decline (OR = 0.99; 95% CI = 0.68-1.44). In conclusion, in this prospective study higher serum total IGF-I levels and higher total IGF-I/IGFBP-3 ratios, but not higher free IGF-I levels, were associated with less cognitive decline over the following 2 yr. Circulating total IGF-I levels may reflect an underlying biological process that influences cognitive decline.

Aged↗
PubMed1998

Insulin-like growth factor I receptors on blood cells: their relationship to circulating total and "free" IGF-I, IGFBP-1, IGFBP-3 and insulin levels in healthy subjects.

The relationships between the insulin-like growth factor I/insulin-like growth factor binding protein (IGF-I/IGFBP) system and the IGF-I receptor characteristics on erythrocytes and PBMCs in healthy subjects in the fasting state were studied to establish whether this would be a valid way of examining IGF-I receptors in vivo. The K(d) of the IGF-I receptor on erythrocytes was positively related to circulating "free" IGF-I levels. For the IGF-I receptor on PBMCs no relationship was observed with "free" IGF-I levels. IGFBP-3 levels were inversely related to the number of IGF-I binding sites on erythrocytes and to the K(d) of the IGF-I receptor on PBMCs. Total IGF-I, insulin and IGFBP-1 levels showed no relation to the IGF-I receptor on erythrocytes and PBMCs in the fasting state. This report suggests that studies of IGF-I receptor characteristics on erythrocytes and PBMCs in the fasting state are cell-specific and cannot be extrapolated to other cell types, which may be more relevant target tissues for IGF-I action in vivo.

Adult↗
PubMed1998

Serum free IGF-I, total IGF-I, IGFBP-1 and IGFBP-3 levels in an elderly population: relation to age and sex steroid levels.

BACKGROUND: Most previous studies concerning the relationship between IGF-I and age used assays measuring total IGF-I. Although free IGF-I is considered of greater biological relevance, little is known about its relationship with sex steroids levels in elderly healthy subjects. MEASUREMENTS: In a cross-sectional study of 218 healthy people (103 men, 115 women) aged 55-80 years we measured serum total and free IGF-I, IGFBP-1 and IGFBP3 levels and sex steroids. Free androgen index and free oestradiol index were used as an indicator for free oestradiol and free testosterone levels, respectively. RESULTS: Free IGF-I levels did not decline with age in the whole study population. Free IGF-I levels even increased in individuals above 70 years of age in comparison to those aged between 55 and 70 years (mean +/- SE 0.106 +/- 0.007 nmol/l vs. 0.086 +/- 0.004 nmol/l, P = 0.009). Total IGF-I and IGFBP-3 decreased with age (r = -0.20, P = 0.005 and r = -0.24, P = 0.001, respectively). Total IGF-I levels were positively related with free oestrogen index in both sexes. Free IGF-I did not relate to free oestrogen or androgen index. In women only, free IGF-I was related positively with DHEAS while IGFBP-1 was inversely correlated with DHEAS. CONCLUSIONS: Free IGF-I levels do not decrease with age and are even higher in individuals above 70 years. There was no relationship between free IGF-I and free androgen or oestrogen index in either gender. We hypothesize that higher free IGF-I levels in older persons may be the consequence of selective survival in the cohort: subjects with high free IGF-I levels may live longer. The absence of a relationship between free IGF-I levels and free androgen and oestrogen indices suggests that there is no direct interaction between the biological activity of circulating IGF-I levels and sex hormone production in a healthy ageing population.

Age Factors↗
PubMed1998

The acute effect of dexamethasone on plasma leptin concentrations and the relationships between fasting leptin, the IGF-I/IGFBP system, dehydroepiandrosterone, androstenedione and testosterone in an elderly population.

OBJECTIVE: To investigate the acute effect of dexamethasone administration on serum leptin levels and the relationships between dehydroepiandrosterone (DHEAS), androstenedione, testosterone and the IGF-I/IGFBP system and leptin levels in healthy elderly humans. METHODS: In 209 healthy elderly individuals (95 men, 114 women, aged 55-80 years) measurements were made in the fasting state (0800 h) and after an overnight dexamethasone suppression test (1 mg p.o. at 2300 h. RESULTS: Mean leptin levels increased from 6.2 +/- 0.4 (SE) micrograms/l to 7.3 +/- 0.5 (SE) micrograms/l in men and from 18.9 +/- 1.4 (SE) micrograms/l to 23.9 +/- 1.8 (SE) micrograms/l in women after 1 mg dexamethasone overnight ('post treatment')(P < 0.001 for both sexes). There was a significant relationship between post-treatment leptin and dexamethasone levels (men: P = 0.002; women: P < 0.001). The increase in leptin levels after dexamethasone administration was only partially related to the increase in plasma insulin concentrations. Cortisol levels were not related to leptin. In multivariate analyses the relationship between post-treatment leptin and dexamethasone levels remained after adjustment for post-treatment insulin levels, BMI, waist:hip ratio (WHR) and age (men: P < 0.001; women: P = 0.001). Plasma (free and total) IGF-I and IGFBP-3 levels were not related to leptin levels in men or women. IGFBP-1 levels were inversely related to leptin levels (P = 0.02), but this relationship was lost after adjustment for insulin, and/or BMI. In multivariate analyses the relationship between leptin and DHEAS was inverse in women (P = 0.04) (after adjustment for BMI, WHR, insulin and glucose), while there was no relationship between leptin and DHEAS in men. CONCLUSIONS: Administration of dexamethasone acutely increased leptin levels within 9 h in this elderly population. This increase was only partly related to changes in circulating insulin concentrations, but was independent of BMI and waist:hip ratio. No relation existed between leptin and (free or total) IGF-I and IGFBP-3 in men or women. Dehydroepiandrosterone was inversely related to leptin in women. These findings suggest a contributory regulatory role for corticosteroids in modulating circulating leptin concentrations in elderly healthy individuals of both sexes, which is at least in part independent of insulin, BMI and waist:hip ratio. Dehydroepiandrosterone might play a role in the gender-specific differences in serum leptin levels.

Aged↗
PubMed1998

Lack of associations between serum leptin, a polymorphism in the gene for the beta 3-adrenergic receptor and glucose tolerance in the Dutch population.

BACKGROUND: The associations between leptin levels and the prevalence of a polymorphism in the beta 3-adrenergic receptor were studied in a cross-sectional analysis of 600 participants in a population-based study, which were stratified for glucose tolerance by an oral glucose tolerance test. METHODS: In a random sample of 600 participants in the Rotterdam study, aged 55-75 years at baseline (309 men, 291 women) the relationships were studied between the presence of Trp64 Arg mutation in the beta 3-adrenergic receptor gene and fasting leptin, glucose and insulin (fasting and after an oral glucose load), and other components of the insulin resistance syndrome. RESULTS: Mean age of the study population was 66.9 years (SD 5.7). Fasting serum leptin levels overall in men and women were 6.1 micrograms/l (SE 0.2) and 21.7 micrograms/l (0.9), respectively, (P < 0.001). These differences were independent of age, body mass index and waist to hip ratio. We identified 73/600 persons who were heterozygotes for the Trp64 Arg polymorphism (allelic frequency 6.1%), but failed to find an association between the presence of this polymorphism and leptin or any measured parameter indicative for obesity, impaired glucose tolerance or type 2 diabetes mellitus. CONCLUSION: Heterozygosity for the Trp64Arg polymorphism of the beta 3-adrenergic receptor gene is not accompanied by obesity, impaired glucose tolerance and type 2 diabetes mellitus in the general elderly Dutch population, and is also not associated with changes in circulating leptin levels.

Aged↗
PubMed1998

The IGF-I/IGFBP system in congenital partial lipodystrophy.

BACKGROUND AND OBJECTIVES: Insulin and IGF-I interact at many levels. Little is known about the insulin-like growth factor-I/insulin-like growth factor binding proteins (IGF-I/IGFBP) system in congenital partial lipodystrophy, a syndrome characterized by insulin resistance, hyperinsulinaemia and absence of truncal and limb fat. Some cases have acromegaloid features with thick skin and large hands and feet in association with normal levels of circulating growth hormone. METHODS: In four females known with congenital partial lipodystrophy, hyperinsulinaemia with acromegaloid features, the number and affinity of the IGF-I receptors on peripheral blood mononuclear cells (PBMCs), and the concentration of circulating insulin, total and free IGF-I, IGFBP-1 and IGFBP-3 levels were measured in the fasting and the fed state. Cultures of PBMCs of the patients with lipodystrophy were also used to study the effect of IGF-I stimulation on thymidine uptake in vitro. MEASUREMENTS: In the subjects with lipodystrophy the affinity and the number of the IGF-I receptors on peripheral mononuclear cells (PBMCs) and erythrocytes did not differ significantly from controls in the fasting state. Insulin levels were significantly higher in subjects with lipodystrophy both in the fasting as well in the fed state. Total IGF-I, free IGF-I and IGFBP-3 levels did not differ but serum IGFBP-1 levels were lower in lipodystrophy subjects than in healthy controls. The free IGF-I/IGFBP-1 ratio was increased in lipodystrophy subjects both in the fasting and the fed states. The effects of IGF-I stimulation on thymidine uptake by PBMCs of lipodystrophy subjects in the absence of IGFBP-1 were not different from healthy controls cultures in vitro. When a combination of IGFBP-1 (in a concentration comparable to the fasting serum IGFBP-1 levels in lipodystrophy patients found in our study) and IGF-I was added to PBMC cultures from lipodystrophy patients no decrease in thymidine uptake by PBMCs was found. CONCLUSIONS: In the four subjects with lipodystrophy hyperinsulinaemia, lowered free IGF-I and IGFBP-1 levels, but increased free IGF-I/IGBP-1 ratios were observed. Low IGFBP-1 concentrations in culture media did not reduce the stimulating IGF-I effect on thymidine uptake by PBMCs from lipodystrophy patients. Our data suggest that the observed increased IGF-I/IGFBP-1 ratio in lipodystrophy patients contributes to an unopposed biological effect of IGF-I on IGF-I receptors, thereby inducing the development of acromegaloid features, acanthosis nigricans and polycystic ovaries in some patients with congenital partial lipodystrophy.

Adult↗
PubMed1998

Serum free and total insulin-like growth factor-I, insulin-like growth factor binding protein-1 and insulin-like growth factor binding protein-3 Levels in healthy elderly individuals. Relation to self-reported quality of health and disability.

BACKGROUND: Little is known about the influence of the free insulin-like growth factor-I/insulin-like growth factor binding protein (IGF-I/IGFBP) system on the quality of health and on disability in the elderly population. DESIGN: In a cross-sectional population based study of 218 healthy elderly subjects (age 55-80 yrs) fasting free and total insulin-like growth factor (IGF-I), insulin-like growth factor binding protein-1 (IGFBP-1) and insulin-like growth factor binding protein-3 (IGFBP-3) levels were measured. Subjective quality of health was assessed by asking all participants whether they judged the quality of their health as better, the same or worse than that of their peers. Disability was determined by the Disability Index of the Stanford Health Questionnaire. RESULTS: Mean serum-free IGF-I levels were significantly lower in the 21 subjects who experienced their health as worse than those of their peers, compared to the 181 subjects who experienced their health as better or the same as their peers 0.069 (SE 0.009) vs. 0.093 nmol/l (SE 0.004) (p = 0.04). Mean IGFBP-1 levels were significantly higher in subjects, who felt less healthy than their peers 1.23 (SE 0.26) vs. 0.73 nmol/l (SE 0.82) (p = 0.01). Free and total IGF-I, IGFBP-1 and IGFBP-3 levels, were not different in subjects with the lowest and the highest Disability Index Score. CONCLUSION: Low free IGF-I and high IGFBP-1 levels are associated with a decreased self-reported quality of health, but are not related to physical disability in the elderly.

Aged↗