Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate whether previously reported increased levels of insulin-like growth factor-binding protein-1 (IGFBP-1) in GH-deficient patients only reflect decreased levels of insulin or are elevated in relation to insulin, diurnal profiles of IGFBP-1 and insulin were determined in plasma from patients with GH levels below 0.2 microgram/L throughout 24 h (n = 23) and compared to profiles from patients with insulin-dependent diabetes mellitus (IDDM; n = 9) and healthy subjects (n = 12). Samples were drawn using a continuous withdrawal technique at 20-min intervals. Levels of IGF-I were determined in one morning sample. As in healthy subjects, serum IGFBP-1 displayed a diurnal variation in GH-deficient as well as in IDDM patients, with lowest levels in the afternoon and evening and a rise with maximum levels during the night and morning. Fasting and 24-h mean levels of IGFBP-1 were significantly higher in GH-deficient patients [61 +/- 12 (P < 0.01) and 39 +/- 6 micrograms/L (P < 0.01), respectively] and IDDM patients [72 +/- 18 (P < 0.01) and 45 +/- 9 micrograms/L (P < 0.01), respectively] compared to those in healthy subjects (27 +/- 4 and 18 +/- 2 micrograms/L, respectively). Fasting levels of IGFBP-1 correlated to 24-h mean values of IGFBP-1 in all groups separately and in the combined group (r = 0.931; P < 0.001). An inverse relationship was found between IGFBP-1 and insulin in GH-deficient patients, both between 24-h mean values (r = -0.756; P < 0.001) and between fasting values (r = -0.721; P < 0.001). Corresponding values for healthy subjects were r = -0.548; P = 0.065 and r = -0.712; P < 0.01, respectively, whereas in IDDM patients the relationship was nonsignificant. Moreover, in GH-deficient patients, the diurnal mean levels of IGFBP-1 were inversely correlated to IGF-I (r = -0.477; P < 0.05) and body mass index (r = -0.450; P < 0.05). When insulin was taken into account, a tendency for a negative correlation between IGFBP-1 and IGF-I (P = 0.054) remained, whereas the relationship to body mass index disappeared. However, IGFBP-1 levels were elevated in relation to insulin levels in GH-deficient patients compared to healthy subjects (F = 48.7; P < 0.001 and F = 32.5; P < 0.001, diurnal mean values and fasting values, respectively). The majority of the IDDM patients had values in the same range as the GH-deficient patients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Altered relation between circulating levels of insulin-like growth factor-binding protein-1 and insulin in growth hormone-deficient patients and insulin-dependent diabetic patients compared to that in healthy subjects. 754 95

We evaluated levels of insulin-like growth factor-I and interleukin-1 alpha and beta in patients with pancreatic cancer; the role of these substances in tumor spread and in hyperglycemia was also investigated. Thirty pancreatic cancer patients (21 with hyperglycemia) were compared with others with diseases causing hyperglycemia [liver cirrhosis (14 cases, 12 with hyperglycemia), chronic pancreatitis (20 cases, 12 with hyperglycemia), type I diabetes mellitus (13 cases, all hyperglycemic)]. Insulin-like growth factor-I was significantly reduced in patients with liver cirrhosis, probably due to a reduced hepatic capacity for synthesis. It was increased in 6 of 30 pancreatic cancer patients; in these subjects it was correlated with alanine aminotransferase and C-peptide, but not with tumor diameter or the presence of metastases. Interleukin-1 alpha and beta were both elevated in pancreatic cancer patients. The former was high, while the latter was low when liver metastases were present. Neither was related to glucose or C-peptide levels. In summary, insulin-like growth factor-I levels are increased in some pancreatic cancer patients but this does not seem to favor tumor spread; however IGF-I could be involved influencing glucose homeostasis. Interleukin-1 alpha increased, while interleukin-1 beta decreased in pancreatic cancer patients with metastases, suggesting a different involvement of these two substances in pancreatic cancer spread.
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PMID:Insulin-like growth factor-I, interleukin-1 alpha and beta in pancreatic cancer: role in tumor invasiveness and associated diabetes. 778 9

We have previously demonstrated weekly iv insulin-like growth factor-I (IGF-I; 500 micrograms/kg) bolus therapy to be effective in inducing sustained insulin sensitivity in a patient with type I diabetes mellitus and massive insulin resistance. The present study was undertaken to determine the efficacy of daily sc IGF-I in the treatment of two severely insulin-resistant type I diabetic patients (requiring in excess of 3500 U insulin/day) compared to weekly iv IGF-I therapy. Prolonged insulin sensitivity was achieved in both patients after weekly 500 micrograms/kg iv bolus infusions of IGF-I, with sc insulin requirements falling to approximately 1 U/kg.day. Smaller iv doses (250 micrograms/kg) of IGF-I were ineffective in acutely lowering serum glucose or inducing sustained insulin sensitivity. However, even this smaller IGF-I dose resulted in acute symptomatic hypophosphatemia, which could be prevented by coadministration of potassium phosphate. With sc administered IGF-I (up to 10 mg twice daily), insulin appeared to control patient glucose concentrations, but severe insulin resistance returned within 72 h of discontinuing IGF-I therapy. IGF-I dosing was decreased to the lowest concentration that maintained euglycemia (7.5 mg in the morning and 2.5 mg in the evening). However, severe arthropathy in both patients and neurological symptoms including multiple cranial nerve palsies in one patient were associated with chronic therapy. We conclude that both iv and sc administered IGF-I can precipitate acute symptomatic hypophosphatemia. Chronic low dose sc therapy may be associated with severe neuropathy and arthropathy, and does not induce the sustained insulin sensitivity associated with high dose intermittent bolus IGF-I therapy.
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PMID:High dose intravenous, but not low dose subcutaneous, insulin-like growth factor-I therapy induces sustained insulin sensitivity in severely resistant type I diabetes mellitus. 804 59

This study investigated the effect of IDDM on cartilage anabolic activity in rats. Rats were injected with STZ to induce IDDM, were hypophysectomized, or were injected with STZ and hypophysectomized. After 14 days, control (intact and sham-Hx) and Hx rats were normoglycemic, whereas the rats with IDDM exhibited hyperglycemia and glycosuria. The HxDb rats, however, had normal blood glucose levels and no glycosuria. Both growth, serum levels of IGF-I, and basal cartilage 35SO4 incorporation measured in vitro were decreased in the Hx, IDDM, and HxDb groups. IGF-I added in vitro significantly stimulated 35SO4 incorporation by cartilage explants from control and Hx animals, whereas explants from the animals with IDDM were unresponsive. Explants from the HxDb rats, however, were stimulated by IGF-I in a dose-related manner. Because Hx corrected the glycemic status of the IDDM rats and restored cartilage responsiveness to IGF-I, a second set of experiments was undertaken to further investigate the relationship between cellular metabolism and anabolic activity in cartilage. Cartilage explants from rats fasted for 48 h showed significantly decreased basal 35SO4 incorporation, which was as low as that in explants from rats with severe IDDM. Whereas explants from the IDDM rats were completely unresponsive, those from the fasted rats (and fed rats) were significantly stimulated by the added IGF-I. However, incubation in the presence of 2-D-G, which causes intracellular glucopenia, or in the absence of glucose, completely blocked the anabolic response to IGF-I in otherwise responsive tissues. In conclusion, an important component of diabetic growth inhibition appears to be tissue resistance to the anabolic action of IGF-I, a condition that is correctable by Hx and that may be a result of metabolic impairment at the tissue level.
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PMID:An insulin-like growth factor I-resistant state in cartilage of diabetic rats is ameliorated by hypophysectomy. Possible role of metabolism. 843 17

The objective of this paper was to determine the effect of glycaemic control and endocrine functions on linear growth in children with IDDM. We studied 45 prepubertal children with IDDM (30 males, 15 females) over 1 year period. The mean +/- SD for age of onset and duration of IDDM were 6.2 +/- 2.3 years and 3.5 +/- 1.3 years, respectively. At each clinic visit (every 3 months), glycaemic control was assessed by measuring glycosylated haemoglobin (HbA1C). Growth hormone and cortisol responses to high dose clonidine (0.15 mg/m2) and ACTH, respectively, were evaluated and circulating concentrations of free thyroxine (FT4) and TSH estimated. The average insulin dose (unit/kg/day) during this period was calculated for each patient. Growth was assessed by determining both height standard deviation score (HtSDS) and growth velocity standard deviation scores (GVSDS) and bone age determined according to the atlas of Greulich and Pyle. Two-hundred-and-fifty age- and sex-matched normal children served as controls for growth data, and 20 normal age-matched children and 20 normal children with short stature (NVSS) served as controls for the hormonal studies. Growth velocity (GV) (cm/year) and GVSDS were significantly lower in children with IDDM compared to normal children, and significantly lower in children with poorly controlled diabetes compared to those with good glycaemic control. GV and GVSDS were inversely correlated to HbA1C (r = -0.356, P < 0.01 and r = 0.335, P < 0.01 respectively). GVSDS was correlated with serum IGF-I (r = 0.22, P < 0.01), FT4 (r = 0.321, P < 0.01) and inversely with basal GH (r = -0.362, P < 0.01) concentrations, but was not correlated with cortisol levels or peak GH concentrations in response to clonidine. GVSDS was correlated with HtSDS (r = 0.222, P < 0.01) and inversely with age (r = -0.43, P < 0.05). There was no significant correlation between GVSDS on the one hand and weight gain or body mass index (BMI) on the other hand. Peak GH response to clonidine was correlated with BMI (r = 0.68, P < 0.001) and insulin dose/kg/day (r = 0.602, P < 0.01). This study confirms that in children with IDDM linear growth velocity is dependent on the age of the child and the degree of glycaemic control, as well as on growth promoting hormones such as IGF-I and FT4. High BMI is associated with more GH secretion in response to clonidine, this might explain the higher requirements of insulin/kg in children with IDDM and high BMI.
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PMID:Growth parameters, growth hormone (GH) response to clonidine and circulating insulin-like growth factor-I (IGF-I), free thyroxine (FT4) and cortisol concentrations in relation to glycaemic control in children with insulin-dependent diabetes mellitus. 881 35

Growth hormone (GH) secretion disorders have been reported in poorly controlled type I diabetes mellitus patients. Our work was aimed to evaluate GH secretion in 9 type I young diabetes mellitus patients as well as the low molecular weight IGF-binding protein secretion (IGFBP-1) in 5 of them. The patients did not show any signs of malnutrition or neurovascular complications, neither were they on any medication except for insulin. The study protocol included blood samples collection during a 24-h period for measurement of glucose, glycated hemoglobin, GH IGF-I and IGFBP-1 levels under two situations: on poor glycemic control and after 2-3 months on better control through systematic diet, low in carbohydrates and increase in insulin dosage. GH secretion data were analyzed by Cluster algorithm for pulsatility parameters; for rhythm assessment Cosinor method was used. The first study (poor control) reported significant increase of GH maximal and incremental amplitude and duration pulse values, when compared to the second study (better control). Mean 24-h secretion values as well mean GH for interpulse intervals (valleys) decreased, although not statistically significant. The fraction of pulsatile GH/24 h GH did not change significantly with better glycemic control. No changes in pulse frequency were observed. Mean IGF-I concentrations were significantly higher when patients were on better glycemic control. An ultradian variation for GH secretion was noticed in the first study (poor control) and a circadian variation in the second one (better control). IGFBP-1 analysis showed significant decrease of the mean 24-h values under better glycemic control. Linear regression analysis demonstrated a correlation between IGFBP-1 levels and fasting glucose levels. A circadian variation was present in IGFBP-1 secretion, irrespective of glycemic control. Therefore, we concluded that for type I diabetic patients: 1. GH secretion is increased on poor control, through maximal, incremental amplitude and pulse duration values; 2. IGFBP-1 values were significantly reduced and IGF-1 levels significantly higher after better glycemic control; 4. GH ultradian secretion is reported on poor control, and circadian on the better one, 5. IGFBP-1 circadian secretion occurred irrespective of glycemic control.
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PMID:Effect of glycemic control on growth hormone and IGFBP-1 secretion in patients with type I diabetes mellitus. 888 37

Pubertal development has recently been evaluated from the standpoint of changes in insulin-like growth factor (IGF)-I and IGF-binding protein-3 (IGFBP-3) levels in healthy children. We studied puberty related changes in serum IGF-I and IGFBP-3 levels in 24 patients (11 prepubertal) with insulin dependent diabetes mellitus (IDDM) and 26 healthy subjects (14 prepubertal). Serum IGF-I and IGFBP-3 levels were assayed using immunoradiometric assays and radioimmunoassays, respectively. Serum IGF-I and IGFBP-3 levels in diabetics did not increase during puberty, as opposed to those in healthy children. Serum IGF-I and IGFBP-3 levels of diabetic patients were found to be lower than those of control subjects during puberty (p < 0.0001 and p < 0.05, respectively). Proteolysis is believed to be a general mechanism to increase IGF bioavailability in the presence of IGFBPs. Increased IGFBP-3 protease activity has been shown in sera of children with IDDM as well as a decrease in this activity in response to insulin therapy. Our data displaying low IGFBP-3 levels in diabetic children may be due to increased proteolysis, which also causes a shift in IGF-I to its lower molecular weight forms. Higher rate of clearance of the latter may be the reason for the low IGF-I levels we observed in children with IDDM. The moderate correlation between insulin dose and IGFBP-3 levels (r = 0.5, p < 0.01) may suggest insulin to be a contributing factor in the regulation of IGFBP-3 levels. We conclude that regulation of IGF-I and IGFBP-3 concentrations is disturbed in children with IDDM, in particular during adolescence.
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PMID:Serum levels of insulin-like growth factor-I and insulin-like growth factor binding protein-3 in children with insulin-dependent diabetes mellitus. 891 Aug 17

To evaluate the role of insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) in excessive fetal growth (macrosomia) in diabetic pregnancy, 84 insulin-treated diabetic mothers and their infants were tested for serum concentrations of IGF-I, IFG-II, and IGFBP-1, -2 and -3. These parameters were correlated with the birth weight of neonates and placental weight. IGF-I and II levels were determined by specific radioimmunoassays (RIAs) after serum samples were extracted with aid-ethanol. IGFBPs were measured by Western immunoblot with specific antibodies to the respective IGFBP species. Serum concentrations of both IGF-I and IGF-II in mothers with either IDDM or NIDDM increased with the gestational period, reached a plateau at the third trimester, and returned to non-pregnant levels within 7 days after delivery. These values were not different from those in normal mothers before and throughout pregnancy. As previously reported, IGF-I concentrations in cord serum of neonates born to diabetic mothers were (P < 0.01) higher than those of newborns of normal mothers. Likewise, cord blood IGF-II levels were 2-fold higher in babies of diabetic mothers (P <0.001). Fetal IGF-I and IGF-II correlated with each other and with maternal HbA1C, and they positively correlated with either birth weight or placental weight. Cord IGFBP-3 concentrations were significantly higher in diabetic pregnancy, but IGFBP-2 concentrations were not different from those in normal pregnancy. Cord IGFBP-1 concentrations were significantly higher only in babies of mothers with IDDM. None of these cord IGFBP concentrations correlated with birth weight or placental weight. The data suggest that fetal IGF-II, like IGF-I, is involved in fetal and placental growth in diabetic pregnancy. The role of IGFBPs remained to be determined.
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PMID:Insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBP-1, -2 and -3) in diabetic pregnancy: relationship to macrosomia. 902 69

The structure of IGF-I is similar to that of insulin, having 43% sequence homology with human proinsulin. Both peptides can induce metabolic and mitogenic effects through their own specific receptors, which also share many structural and functional similarities. Primarily involved in the regulation of growth, IGF-I may have a role in the control of glucose homeostasis, facilitated by changes in its binding proteins. RhIGF-I can reduce hyperglycaemia in patients with severe insulin resistance by direct effects mediated via the IGF-I receptor. Improvements in insulin sensitivity, and reductions in blood glucose levels and HbA1c values have also been seen in subjects with NIDDM. Enhanced insulin sensitivity with low dose rhIGF-I has been observed in adolescents and young adults with IDDM. These effects are closely related to reductions in growth hormone levels, but there is also evidence of complex interactions with insulin at the post receptor level and with IGFBP-1. In recent randomised, double-blind, placebo controlled trials, rhIGF-I given as an adjunct to insulin therapy reduced to HbA1c values. Although the ideal dosage to obtain therapeutic efficacy without complications has yet to be determined, rhIGF-I may have an important role in the treatment of hyperglycaemia and insulin resistance in diabetes.
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PMID:Does recombinant human insulin-like growth factor-1 have a role in the treatment of diabetes? 930 Feb 21

To investigate whether recombinant human insulin-like growth factor-I (rhIGF-I) has direct effects on the insulin requirement to maintain euglycemia independent of the growth hormone (GH) level, nine subjects with insulin-dependent diabetes mellitus ([IDDM] seven females; median (range) age, duration of diabetes, and hemoglobin A1C [HbA1C], 16.9 (12.5 to 21.9) years, 11.8 (4.6 to 16.8) years, and 9.8% (7.9% to 14.1%), respectively) underwent two euglycemic studies (6:00 PM to 8:00 AM) after double-blind subcutaneous administration of rhIGF-I/placebo (40 microg/kg). Octreotide infusion (300 ng/kg/h) suppressed endogenous GH, and three identical discrete GH pulses were infused on both nights. Variable-rate insulin infusion maintained euglycemia. Samples were taken every 15 minutes (glucose and GH), 30 minutes (insulin and intermediate metabolites), and 60 minutes (IGF-I and nonesterified fatty acids [NEFA]). Variables were analyzed during the steady-state period of euglycemia (4:00 to 8:00 AM). Data are expressed as the mean +/- SEM. The insulin infusion rate and free-insulin level were both significantly reduced after rhIGF-I administration (0.13 +/- 0.03 v placebo 0.23 +/- 0.05 mU/kg/min, P = .04, and 8.4 +/- 1.3 v placebo 12.1 +/- 1.4 mU/L, P = .03, respectively). GH pulse-related changes in the insulin requirement observed after placebo were not present after rhIGF-I. Glucagon levels were equally suppressed on both nights. Insulin clearance was not altered after rhIGF-I administration. NEFA and ketone levels also were not different on the 2 nights. In conclusion, in adolescents and young adults with diabetes, rhIGF-I administration directly affected insulin requirements independent of GH levels, but had no effect on fatty acid or ketone levels. This difference is related to the abolition of changes in the insulin requirement after GH pulses, and would suggest a complex interaction between GH and IGF-I on insulin action.
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PMID:Recombinant human insulin-like growth factor-I abolishes changes in insulin requirements consequent upon growth hormone pulsatility in young adults with type I diabetes mellitus. 944 Apr 74


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