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K Brismar

Publications and source records attributed to K Brismar.

At least 37 records · Page 2Linked to original sources
PubMed2002

Elevated intraocular levels of insulin-like growth factor I in a diabetic patient with acromegaly.

Growth factors have become increasingly associated with various events of vitreoretinal disease. In the presence of proliferative retinopathy, elevated levels of insulin growth factor I (IGF-I) have been demonstrated in the vitreous. IGF-I expression itself is regulated by growth hormone, a hormone that is involved in the pathogenesis of acromegaly. In the present paper we report on the detection of very high IGF-levels in the subretinal fluid of a patient with acromegaly who was operated for retinal detachment. With a very sensitive RIA assay we found a four-fold elevation of the serum levels of IGF-I (604 ng/ml) and a high level of IGF-1 in the subretinal fluid (13 ng/ml). It is concluded that acromegaly may lead to an overexpression of IGF-I not only seen as increased concentrations in serum and vitreous, but in the subretinal space as well. This study emphasizes the need for further investigation of growth factor presence in pathological cavities, such as the subretinal space during retinal detachments.

Acromegaly↗
PubMed2001

A strong association between biologically active testosterone and leptin in non-obese men and women is lost with increasing (central) adiposity.

OBJECTIVE: In both humans and rodents, males have lower levels of leptin than females at any level of adiposity. Experimental data support the idea that testosterone exerts a negative influence on leptin levels. There are, however, major inconsistencies in available data concerning the possible association between androgenicity and leptin in humans. Reasons could be the influence of androgenicity on leptin production being dependent on body composition, and incomplete measures of biologically active testosterone levels. In the present study we have characterized the relationship between biologically active testosterone and leptin after careful stratification for gender and adiposity. DESIGN AND SUBJECTS: Healthy subjects (n=158; 85 men and 73 pre- and postmenopausal women) from the Northern Sweden MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) population were studied with a cross-sectional design. MEASUREMENTS: Anthropometric measurements (body mass index (BMI) and waist circumference) and oral glucose tolerance tests were performed. Circulating levels of leptin, insulin, testosterone, androstenedione, sex hormone-binding globulin (SHBG) and insulin-like growth factor-1 (IGF-1) were measured by radioimmunoassays or microparticle enzyme immunoassays. Apparent concentrations of free testosterone and non-SHBG-bound testosterone were calculated. RESULTS: After adjustments for age, BMI and insulin, leptin levels were inversely correlated to testosterone levels in non-obese men (r=-0.56, P<0.01) and obese women (r=-0.48, P<0.05). In contrast, leptin and testosterone correlated in a positive manner in non-obese women (r=0.59, P<0.01). Levels of SHBG were negatively associated with leptin in men with low waist circumference (r=-0.59, P<0.01). The following factors were associated with leptin in a multivariate model: low levels of biologically active testosterone and SHBG in men with low and medium waist circumference, insulin in men with high waist circumference, high levels of testosterone and insulin in non-obese women, and BMI in obese women. CONCLUSION: We conclude that low leptin levels are associated with androgenicity in non-obese men and women and that the direction of this association is dependent on gender and body fat distribution. Based on these results we suggest that the relation between testosterone and leptin contributes to the gender difference in circulating leptin levels. International Journal of Obesity (2001) 25, 98-105

Adipose Tissue↗
PubMed2001

Alcohol ingestion decreases both diurnal and nocturnal secretion of leptin in healthy individuals.

OBJECTIVE: Neuropeptide Y (NPY) stimulates appetite and increases food intake. Leptin inhibits NPY. It is not known whether alcohol influences any of these factors, but it has been suggested that alcohol stimulates appetite in man. The primary objective of this investigation was to determine whether ingestion of ethanol inhibits leptin secretion in normal subjects. SUBJECTS AND DESIGN: Fourteen healthy, non-obese subjects of both sexes (7 F/7 M) were included. They were divided into two groups (I and II; 8/6). All were investigated on two occasions. On one occasion alcohol was ingested, and on the other drinking water was given. The experiments took place in random order, one week apart. In group I two experiments (A = alcohol; B = water) were performed during the day. In group II the experiments were carried out during the night (C = alcohol; D = water). Each alcoholic drink contained 0.45 g ethanol/kg. The drinks were given at 08.00, 09.30 and 11.00 hours in experiments A and B, and at 18.00, 20.00 and 22.00 hours in experiments C and D. Venous blood samples were collected before, during and after the drinks over periods of 6 h in group I and 14 h in group II. MEASUREMENTS: Serum concentrations of leptin, insulin-like growth factor 1 (IGF-1), IGF binding protein 1 (IGFBP-1), insulin, cortisol, testosterone, ethanol and plasma glucose were determined. RESULTS Group I serum leptin levels declined during the day in both men and women regardless of whether alcohol or water had been administered in the morning. Since leptin levels in general were markedly higher in women than in men, all leptin changes after water/alcohol were transformed to percentage changes to make them comparable between sexes. When the percentage leptin decline over a 6-h period (08.00-24.00 hours) was expressed by a decremental area under curve (AUC08-14), it became evident that alcohol inhibited leptin secretion, inasmuch as the leptin decremental area, obtained after alcohol, was significantly larger than the one obtained after water (124 +/- 17 vs. 57 +/- 8; P < 0.01). Similar insulin and glucose levels were obtained after alcohol and water. Group II serum leptin levels increased after both alcohol and water during the initial part of the night (18.00-20.00 hours). In this period alcohol inhibited the secretion of leptin as shown by the leptin incremental area (AUC18-24) which was 53 +/- 18 after alcohol and 113 +/- 15 after water (P < 0.01). As the ethanol concentration in serum began to fall, its inhibitory effect on leptin gradually disappeared, and when leptin AUCs representing the entire night were determined after alcohol and water, they were not significantly different. Similar insulin, glucose, testosterone, IGF-1 and cortisol levels were found after alcohol and water. The IGFBP-1 level increased, but not significantly so until 6 h after commencing the alcohol ingestion. CONCLUSION: Ingestion of moderate amounts of alcohol has an inhibitory effect on leptin secretion in normal subjects. The effect may be direct rather than indirect, since several factors known to affect leptin are not influenced by alcohol. It is tempting to speculate that alcohol might serve as an appetizer by decreasing leptin secretion, but additional studies are necessary to prove that hypothesis since previous studies have shown that leptin has a long-term rather than an acute effect on hunger.

Administration, Oral↗
PubMed2001

Responses of insulin-like growth factor (IGF)-I and IGF-binding proteins to nutritional status in peroxisome proliferator-activated receptor-alpha knockout mice.

Peroxisome proliferator-activated receptor alpha (PPARalpha) plays a central role in glucose and lipid homeostasis. Mice lacking PPARalpha(-/-) have a sexually dimorphic phenotype. We have characterized the IGF system in wild type and PPARalpha-/- mice. In normal mice fasting IGF-I and the IGFBP-3 ternary complex were 2-fold higher in males than in females. PPARalpha influenced the IGF/IGFBP response to feeding, particularly in males. Compared to wild type, male PPARalpha-/- mice had 40% lower total fasting IGF-I concentrations, decreased ALS and less IGFBP-3 ternary complex formation, but within 4 h of refeeding there was an increase in IGF-I and IGFBP-3 ternary complex to values similar to controls. Circulating IGFBP protease activity was induced in male PPARalpha-/- mice during refeeding. IGFBP-1 and insulin concentrations were higher in males than females, and were increased by PPARalpha knockout, suggesting significant hepatic insulin resistance. We speculate that gender differences in the IGF system contribute to the PPARalpha-/- phenotype.

Animals↗
PubMed2001

Day-to-day variability of transcutaneous oxygen tension in patients with diabetes mellitus and peripheral arterial occlusive disease.

PURPOSE: We evaluated the day-to-day variability of transcutaneous oxygen tension (tcPO2) in patients with diabetes mellitus and peripheral arterial occlusive disease who were at risk for chronic foot ulceration. METHODS: The tcPO2 was measured in the morning once daily for 3 consecutive days in 10 male patients with diabetes mellitus who were hospitalized. The mean age of the patients was 65 +/- 13 years, and they had a mean duration of diabetes mellitus of 33 +/- 6 years. The tcPO2 was measured at a reference point at the chest (I2 dx), the dorsum of the foot, and in the first intermetatarsal space. Measurements of tcPO2 in the first intermetatarsal space were performed before and during inhalation of 100% oxygen. RESULTS: The mean tcPO2 was higher (P <.001) at I2 dx (56 +/- 10 mm Hg) than at the dorsum of the foot (25 +/- 19 mm Hg) and first intermetatarsal space (27 +/- 20 mm Hg). tcPO2 increased (P <.001) during inhalation of 100% oxygen, whereas the increase was severely reduced in three patients with tcPO2 less than 10 mm Hg at baseline. A reasonably good day-to-day variability of tcPO2 was seen; the linear relations between tcPO2 investigated on days 1, 2, and 3 were highly significant (P =.0001) at each measuring site, and no systematic differences were seen between the repeated measurements (analysis of variance; P =.13 to.85). CONCLUSION: The results show an acceptable day-to-day variability of tcPO2, both at baseline and during oxygen inhalation, in patients with diabetes mellitus and peripheral arterial occlusive disease.

Aged↗
PubMed2001

Insulin infusion increases levels of free IGF-I and IGFBP-3 proteolytic activity in patients after surgery.

We have studied the effects of insulin on the bioavailability of insulin-like growth factor (IGF) I in insulin-resistant patients after surgery. Serum levels of total IGF-I (tIGF-I), free IGF (fIGF)-I, fIGF-II, and IGF-binding protein (IGFBP) 1 and IGFBP-3 proteolytic activity (IGFBP-3-PA), determined on the day before surgery and on the 1st postoperative day, were related to insulin sensitivity measured by a hyperinsulinemic, normoglycemic clamp. Before surgery, the decreased tIGF-I (P < 0.05) in response to insulin infusion was accompanied by an 18% reduction of IGFBP-1 (P < 0.001), while IGFBP-3-PA remained unchanged. Levels of fIGF-I and fIGF-II were not changed by insulin infusions. After surgery, IGFBP-3-PA increased (P < 0.05) during insulin infusion, and this was associated with an increase in tIGF-I (P < 0.001) and fIGF-I (P < 0.01), while no significant change was found in fIGF-II. The reduction in IGFBP-1 in response to insulin infusion was not affected by surgery. The change in IGFBP-3-PA during insulin infusion after surgery was related to the corresponding change in fIGF-I (r(2) = 0.26, P < 0.05) and postoperative insulin sensitivity (r(2) = -0.22, P < 0.05). These data suggest that increased IGFBP-3-PA during insulin infusion after surgery governs the increased levels of fIGF-I, while insulin-induced suppression of IGFBP-1 was not affected by surgery. We propose that, in catabolic, postoperative patients, increased levels of insulin from exogenous or, possibly, endogenous sources (nutritionally induced) may be a signal to increase IGF-I bioavailability by increased expression of IGFBP-3-PA to counteract further deterioration in glucose metabolism.

Adult↗
PubMed2001

Circulating IGF binding protein-1 is inversely associated with leptin in non-obese men and obese postmenopausal women.

OBJECTIVE: Hyperleptinaemia and hyperinsulinaemia interrelate to insulin-like growth factor binding protein 1 (IGFBP-1), and disturbances in the growth hormone-IGF-I axis are linked to obesity and cardiovascular diseases. However, whether the association between leptin and the GH-IGF-I axis is altered with increasing obesity is not known. We therefore examined the relationship between leptin, IGF-I, IGFBP-1, insulin and proinsulin in men and women with or without obesity in a population study. DESIGN AND SUBJECTS: Healthy subjects (n=158; 85 men and 73 pre- and postmenopausal women) from the Northern Sweden MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) population were studied with a cross-sectional design. METHODS: Anthropometric measurements (body mass index (BMI) and waist circumference) and oral glucose tolerance tests were performed. Radioimmunoassays were used for the analyses of leptin, IGF-I and IGFBP-1, and ELISAs for specific insulin and proinsulin. RESULTS: Leptin inversely correlated to IGFBP-1 in non-obese men (P<0.05) and obese postmenopausal women (P<0.05). In contrast, leptin did not correlate to IGF-I. IGFBP-1 was also significantly associated with proinsulin in non-obese men (P<0.01) and non-obese premenopausal women (P<0.05). The association between leptin and IGFBP-1 was lost after adjustment for insulin. In multivariate analyses taking measures of adiposity into account, low proinsulin, and IGF-I in combination with old age, but not leptin, predicted high IGFBP-1 levels. CONCLUSIONS: Leptin was inversely associated with IGFBP-1 in non-obese men and obese postmenopausal women, and proinsulin was inversely associated with IGFBP-1 in non-obese men and premenopausal women. However, these associations were lost with increasing central obesity in men and premenopausal women and after control for insulin. Therefore, this study suggests (i) that leptin is of minor importance for regulation of IGFBP-1 levels and (ii) that the insulin resistance syndrome is characterised by an altered relationship between leptin, IGFBP-1 and insulin.

Adipose Tissue↗
PubMed2001

Lithium chloride inhibits the expression and secretion of insulin-like growth factor-binding protein-1.

Insulin-like growth factor-binding protein-1 (IGFBP-1) regulates IGF availability for glucose homeostasis. The IGFBP-1 promoter shares common regulatory response elements with phosphoenol pyruvate carboxykinase (PEPCK), the expression and activity of which is inhibited by lithium chloride, associated with an inhibition of glycogen synthase kinase (GSK)-3 activity, in the rat hepatoma cell line H4-II-E. We therefore determined the effect of lithium chloride on IGFBP-1 expression and secretion in H4-II-E cells. Lithium chloride inhibited IGFBP-1 secretion in a dose response and reversible manner by approx 80% during 5-h and 16-h incubations. An inhibitory effect on IGFBP-1 mRNA expression was observed at 2 h. The inhibitory effect of lithium and insulin were not additive when used alone, but inhibition by lithium occurred when insulin action was blocked by activating AMP-activated protein kinase with 5-aminoimidazole-4-carboxamide-riboside (AICAR). These findings suggest that GSK-3 inhibition, or another pathway activated by lithium, may be involved in a pathway controlling IGFBP-1, inhibiting synthesis when insulin activity is absent or impaired.

Animals↗
PubMed2001

Anticholinergic treatment improves glycaemic control in adolescent girls with insulin-dependent diabetes mellitus.

UNLABELLED: Metabolic control often deteriorates during puberty in girls with insulin-dependent diabetes. It is well accepted that there is an abnormality in the growth hormone (GH)-insulin-like growth factor-I (lGF-I) axis in these girls, resulting in reduced IGF-I levels and elevated GH. As GH antagonizes insulin, attempts have previously been made to reduce excess GH secretion through anticholinergic treatment. However, most of these studies have been performed on adult patients. The aim of the present study was to evaluate the effects of 12 wk of oral anticholinergic treatment with Pirenzepine, 100 mg twice daily, in 16 adolescent girls with diabetes. Serum samples of IGF-I, glycated haemoglobin and fasting IGF-binding protein 1 were analysed at initiation and after 3, 8 and 12 wk of Pirenzepine therapy. Nocturnal urinary GH excretion was also examined. Glycated haemoglobin declined significantly after 3 wk of Pirenzepine therapy (9.8 +/- 0.18 vs 9.2 +/- 0.17; p < 0.001) and was still improved at the end of the study. Unexpectedly, nocturnal urinary GH excretion did not change. Serum IGF-I continuously increased during the study, while IGF-binding protein 1 levels were not significantly altered. CONCLUSION: Anticholinergic treatment with Pirenzepine improves glycaemic control in adolescent girls with diabetes. Although nocturnal urinary GH excretion was unchanged there may still be changes in pituitary GH secretion to explain the improvement. Effects of Pirenzepine on gastrointestinal motility can represent other possible mechanisms behind the improved metabolic control.

Adolescent↗
PubMed2000

Tamoxifen-induced cell death in malignant melanoma cells: possible involvement of the insulin-like growth factor-1 (IGF-1) pathway.

Recent data indicate that the estrogen receptor (ER) blocker tamoxifen (TAM) can induce cell death in malignant melanoma cells. However, as shown in the present study and several other studies melanoma cells usually do not express classical ERs. In the present study we investigated whether the cytotoxic effect of TAM on melanoma cells could depend on interference with the expression or function of the insulin-like growth factor-1 receptor (IGF-1R), a plasma membrane receptor important for cell survival in this tumor cell type. Several melanoma cell lines were included in the analysis. Administration of TAM at a concentration of 15 microm or more resulted in cell death of the melanoma cells within 48 h. TAM treatment was correlated to a slight to moderate inhibition of IGF-1 binding to IGF-1R. Since it has been reported that TAM can increase the release of IGF binding proteins (IGFBPs) we then investigated whether this mechanism could underly the decreased IGF-1 binding. However, we could demonstrate that the amount of released IGFBPs were unchanged or decreased in TAM-treated cells. Whereas TAM did not have any strong effect on IGF-1 binding and the expression of IGF-1R at the cell surface, it was was found to efficently block tyrosine phosphorylation of IGF-1R beta-subunit. Taken together, our data suggest that TAM-induced cytotoxicity of malignant melanoma cells can be due to inactivation of IGF-1R.

Antineoplastic Agents, Hormonal↗
PubMed2000

Serum insulin-like growth factor-I level is independently associated with coronary artery disease progression in young male survivors of myocardial infarction: beneficial effects of bezafibrate treatment.

OBJECTIVES: We investigated whether the effect of bezafibrate on progression of coronary atherosclerosis in the BEzafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) was related to insulin-like growth factor (IGF)-I and glucose-insulin homeostasis. BACKGROUND: BECAIT, the first double-blind, placebo-controlled, randomized, serial angiographic trial of a fibrate compound, demonstrated that progression of focal coronary atherosclerosis in young patients after infarction could be retarded by bezafibrate treatment. METHODS: The treatment effects on serum concentrations of IGF-I and insulin-like growth factor binding protein (IGFBP)-1, as well as on basal and postload glucose and insulin levels, were examined, and on-trial determinations were related to the angiographic outcome measurements. RESULTS: Bezafibrate treatment resulted in a significant reduction of serum IGF-I levels, both at two and five years, and on-trial serum IGF-I levels were directly related to changes in both minimal lumen diameter (r = 0.25, p < 0.05) and mean segment diameter (r = 0.29, p < 0.05). In contrast, none of the available indexes of insulin resistance (homeostasis model assessment estimate, basal and postload plasma insulin concentrations and serum IGFBP-1 levels) were related to the angiographic changes, nor were they significantly affected by bezafibrate treatment. Multiple stepwise regression analysis showed that the relation between on-trial serum IGF-I level and coronary artery disease (CAD) progression was independent of baseline angiographic score, age, body mass index, serum lipoprotein and plasma fibrinogen concentrations and measures of glucose-insulin homeostasis. CONCLUSIONS: IGF-I could be implicated in the progression of premature CAD, and a reduction of serum IGF-I concentration could account partly for the effect of bezafibrate on progression of focal coronary atherosclerosis.

Adult↗
PubMed2000

The hyperinsulinaemic-euglycaemic glucose clamp: reproducibility and metabolic effects of prolonged insulin infusion in healthy subjects.

To examine the reproducibility of the hyperinsulinaemic-euglycaemic clamp technique at mid-physiological hyperinsulinaemia, seven healthy subjects ¿age 50 (25, 59) years [median (range)], body mass index 23.1 (20.8, 25.5) kg.m(-2)¿ were investigated with three 2 h hyperinsulinaemic (60 micromol.l(-1))-euglycaemic (4.5 mmol.l(-1)) clamps performed 48 h and 14 days apart respectively. The third clamp was prolonged to 8 h in order to examine effects on glucose disposal during prolonged clamps. The glucose infusion rates (GIRs) during the three 2 h clamps were 7.41 (4.28, 10.96), 7.26 (5.38, 11. 02) and 6.63 (4.42, 10.3) mg.kg(-1).min(-1), with a median intra-individual coefficient of variation of 5.8 (2.6, 22) %. During the 8 h clamp a highly variable gradual increase in GIR was observed, reaching a plateau between 4 and 5 h at 32 (5, 101) % above the GIR between 1 and 2 h (P<0.05). This increase was correlated inversely with the GIR between 1 and 2 h (r=-0.82; P<0.05), and directly with age (r=0.86; P<0.05). Carbohydrate oxidation measured by indirect calorimetry was stable during the repeated 2 h clamps and the 8 h clamp. Endogenous glucose production measured by infusion of [6, 6-(2)H(2)]glucose was suppressed during the 8 h clamp. The 2 h hyperinsulinaemic-euglycaemic clamp is reproducible at a mid-physiological range of hyperinsulinaemia. If prolonged, it results in a delayed increase in non-oxidative glucose disposal, which is most pronounced in subjects with low insulin sensitivity. The findings underline the importance of selecting age-matched controls in studies of insulin resistance.

Adult↗
PubMed2000

Insulin-like growth factor (IGF)-1 and IGF-binding protein-1 concentrations in serum of normal subjects after alcohol ingestion: evidence for decreased IGF-1 bioavailability.

OBJECTIVE: Both insulin-like growth factor (IGF)-1 and insulin-like growth factor-binding protein (IGFBP)-1 are synthesized by the liver. It is well known that chronic alcohol abuse impairs liver function, but less is known about how an acute intake of moderate quantities of alcohol affects hepatic production of IGF-1 and IGFBP-1. The objective of the present investigation was to study this issue by measuring serum levels of IGF-1 and IGFBP-1 in normal subjects before, during and after ingestion of a moderate dose of ethanol. SUBJECTS AND DESIGN: Eight healthy subjects were tested on two occasions. On one occasion (experiment A), three 150-ml doses of ordinary drinking-water were given at 08.00, 09.30, and 11.00 h. On another occasion (experiment B), three 150-ml drinks of diluted ethanol were given instead of water. Each drink contained 0.45 g ethanol/kg b.w. Experiments A and B were performed in random order, 1 week apart. Blood samples were collected before, during and after the drinks over a period of 7 h (08.00-15.00 h). One blood sample was also drawn at 08.00 h the following day. MEASUREMENTS: Blood glucose and serum concentrations of ethanol, insulin, growth hormone (GH), IGF-1 and IGFBP-1 were determined. RESULTS: When alcohol had been ingested, the serum ethanol concentration rose to a peak value of 28.6 +/- 0.9 mmol/l (mean +/- SEM). The serum IGF-1 level declined significantly toward the end of the 7-h period. The serum IGFBP-1 level increased promptly in response to ethanol, and reached a maximum 2.7 times above basal as the ethanol level peaked. Neither IGF-1, nor IGFBP-1 levels changed significantly after water intake. The IGF-1 : IGFBP-1 ratio declined markedly after ethanol (from 15.7 +/- 3.9 to 3.9 +/- 0.6; P < 0.01), but not after water intake. The blood glucose and serum levels of insulin and GH were unaffected by both ethanol and water. CONCLUSIONS: Ingestion of moderate amounts of alcohol by healthy individuals results in an acute and profound increase in the serum IGFBP-1 level and a protracted and less powerful decline in the IGF-1 level. The mechanism behind the IGFBP-1 increase is probably a direct effect on the liver, since neither insulin, nor glucose or GH concentrations changed significantly in response to the ethanol challenge.

Adult↗
PubMed2000

Increased 24 h mean insulin-like growth factor binding protein-3 proteolytic activity in pubertal type 1 diabetic boys.

Hyperglycaemia and increased variability of blood glucose in pubertal children with type 1 diabetes may be related to increased growth hormone (GH) secretion and insulin resistance. The role of changes in insulin-like growth factor-I (IGF-I) bioavailability for the glycaemic control in these patients has not been completely elucidated. In particular, the possible role of increased IGF binding protein-3 (IGFBP-3) proteolysis reported in other insulin resistant states awaits further characterization. The aims of this study were to assess if hyperglycaemia in children with type 1 diabetes was associated with changes in free dissociable IGF-I (fdIGF-I) and IGF binding protein-3 protease activity (IGFBP-3-PA) and if increased insulin resistance during puberty was associated with changes in IGFBP-3-PA in healthy and diabetic children. In diabetic boys in the period of maximal linear growth (Tanner stage 3, n = 5), the mean level and the variability of IGFBP-3-PA, determined every second hour throughout 24 h, were significantly higher both compared to postpubertal diabetic boys (n = 6; P = 0.003 and P = 0.001, respectively), and to age matched healthy boys (n = 4; P = 0.006 and P < 0.001 respectively). This activation of IGFBP-3-PA was most prominent during the day time. The mean 24 h blood glucose level (determined hourly) was the only parameter studied that significantly predicted the changes in mean 24 h IGFBP-3-PA in the diabetes group. The mean 24 h concentrations of fdIGF-I were decreased in the diabetic boys compared to the healthy controls but statistical significance was only achieved in Tanner Stage 5 (p = 0.03). We speculate that the elevated levels of IGFBP-3-PA in Tanner 3 diabetic boys are related to deteriorated glucose homeostasis and that it may be a compensatory mechanism to attenuate the decrease in fdIGF-I in order to partly restore insulin sensitivity and glycemic control.

Adolescent↗
PubMed2000

Insulin-like growth factor binding protein-1 as glucose regulator in adolescent boys with type 1 diabetes.

UNLABELLED: The aim of the present study was to investigate whether the diurnal variability of B-Glucose is dependent on GH, IGF-I and IGFBP-1 levels, apart from insulin, and if there is any difference between Tanner stages 3 and 5. Five boys in Tanner stage 3 and 6 boys in stage 5 with type 1 diabetes were included. Blood was continuously collected from a cubital vein for 24 h. S-Insulin, S-GH, S-IGF-I and S-IGFBP-1 were analysed. B-Glucose was analysed hourly at bedside. One week before and 1 wk after the 24-h study period the participants performed self-monitoring of blood glucose (SMBG) during normal physiologic conditions. In the 24-h profile of B-Glucose, insulin, IGFBP-1 and GH, we found a significant positive correlation between B-Glucose and log IGFBP-1 (r = 0.5, p = 0.005) and an inverse correlation to insulin (r = -0.5, p = 0.004) but no correlation to logGH (r = -0.04, p = 0.831). In multiple regression analysis, B-Glucose was still significantly correlated to log IGFBP-1, when adjusting for insulin and GH, in Tanner stage 5. We found a difference between Tanner stages 3 and 5 in the variability of B-Glucose over a longer period during normal daily activity (p = 0.02), but not over the 24-h study period. CONCLUSION: We have demonstrated in type 1 diabetes adolescent boys a relationship between simultaneously measured blood-glucose and IGFBP-1 levels independent of the insulin and GH levels, suggesting that the free fraction of IGF-I influences the glucose metabolism.

Adolescent↗
PubMed1999

Nutritional status, insulin-like growth factor-1 and quality of life in elderly women with hip fractures.

AIM: To evaluate nutritional status and its relation to cognitive and physical function and quality of life in elderly female patients with hip fractures. METHODS: Nutritional status was assessed in 42 women (80+/-7 years old) using the body mass index (BMI), triceps skin fold, arm muscle circumference and serum levels of insulin-like growth factor (IGF-1) and its binding protein (BP) IGFBP-1. Handgrip strength was measured. The Short Portable Mental Status Questionnaire was used to assess cognitive function and the Nottingham Health Profile to asses quality of life. RESULTS: Low BMI (<== 20) and reduced IGF-1 and IGFBP-1 levels were detected in 50% of the patients. BMI correlated with IGF-1 (p<< 0.02) and with hand grip strength (P<< 0.001). Hand grip strength correlated with arm muscle circumference (P<< 0.05). Cognitive dysfunction was detected in 18% of the patients, and a correlation was found between cognitive function and BMI (P<< 0.01). The Nottingham Health Profile assessment indicated a lower quality of life in underweight patients as compared to others (P<< 0.05). CONCLUSIONS: Half of the elderly women with hip fractures displayed signs of protein-energy malnutrition. Underweight was associated with reduced serum levels of IGF-1, muscle fatigue, cognitive dysfunction and a low quality of life rating, i.e. a cluster of factors which may unfavourably influence the postoperative course in a large proportion of hip fracture patients.

Activities of Daily Living↗
PubMed1999

Effects of oxytocin on the IGF-axis and some gastrointestinal hormones in ad libitum fed and food-restricted female rats.

The aims of this study were to investigate if administration of oxytocin to ad libitum fed and food-restricted female rats affects weight gain, body fatness, the IGF-axis, and some vagally mediated gastrointestinal hormones, such as gastrin, cholecystokinin (CCK) and somatostatin. Ad libitum fed and food-restricted (receiving 70% of the food intake of the ad libitum fed group) female rats were injected subcutaneously, once a day, for 10 days, with saline (control) or oxytocin (1 mg kg-1 bodyweight). The animals were killed 5 days after the last injection. Oxytocin-treated food-restricted females had more body fat and lower plasma levels of IGF-I, IGFBP-1 and IGFBP-3 compared with saline-treated counterparts. Oxytocin-treated ad libitum fed rats also had lower plasma levels of IGFBP-1 but contained less body fat, compared with saline-treated counterparts. There was no effect of oxytocin treatment on body weight or weight gain in either of the feeding groups. Except for gastrin, which was lower, there was no effect of oxytocin on the gastrointestinal hormones studied. The results indicate that oxytocin treatment influences fat deposition and the IGF-axis in female rats, but that the results are dependent on the nutritional status of the animal.

Animals↗