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)

We have determined the level of phosphorylated insulin-like growth factor binding protein-1 (pIGFBP-1) in serum during two catabolic states: diabetes mellitus and trauma. Human sera were incubated with [125I]IGF-I for 2 h followed by non-denaturing PAGE. [125I]IGF-I/IGFBP-1 complexes from serum co-migrated with a pure p4IGFBP-1 standard. Complex formation was specifically inhibited by unlabeled IGF-I. The migration of IGF-I/pIGFBP-1 complexes was retarded by IGFBP-1 antibodies, but not by antibodies against IGFBP-2 or IGFBP-3. Sera from three severely traumatized patients had up to 12-fold more pIGFBP-1 than sera from age-matched controls. The level of pIGFBP-1 was reduced in all three patients upon hospital discharge. Sera from three patients with insulin dependent diabetes mellitus (IDDM) and severe ketoacidosis (DKA) had more pIGFBP-1 than controls. Administration of insulin to DKA patients lowered the level of pIGFBP-1. The present study shows that IGFBP-1 exists as a free, high affinity, phosphorylated form in vivo during two catabolic states.
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PMID:Phosphorylation of insulin-like growth factor binding protein-1 in patients with insulin-dependent diabetes mellitus and severe trauma. 751 91

Insulin-dependent diabetes mellitus (IDDM) during puberty is associated with a reduction in circulating concentrations of insulin-like growth factor-I (IGF-I) and low IGF bioactivity. Altered levels of the IGF-binding proteins (IGFBPs), including low IGFBP-3 and elevated IGFBP-1, have also been described. These abnormalities have been linked to poor growth and deteriorating blood glucose control. We have therefore examined the effects of recombinant human IGF-I (rhIGF-I) administration on the levels of IGF-I, IGF-II, IGFBP-1, IGFBP-3 and IGF bioactivity in a group of 9 late-pubertal adolescents with IDDM. This was a double-blind placebo controlled study with each individual admitted on two occasions when either rhIGF-I (40 micrograms/kg) or placebo was administered by subcutaneous injection in the thigh at 1800 h. Blood samples were then taken for the subsequent 22 h. The half-life of administered rhIGF-I (12.1-22.2 h) was similar to that previously described in normal subjects. There was a small increase in IGFBP-3 concentrations overnight following rhIGF-I administration when compared to placebo, whereas the levels of IGF-II decreased. Under strict euglycaemic conditions, the relationship between insulin and IGFBP-I did not appear to be affected by rhIGF-I administration although the levels of IGFBP-1 tended to be higher overnight. IGF bioactivity was low during the placebo study, and although within the normal adult range following administration of IGF-I, was still relatively low for adolescents in late puberty.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of recombinant human insulin-like growth factor-I (IGF-I) administration on the levels of IGF-I, IGF-II and IGF-binding proteins in adolescents with insulin-dependent diabetes mellitus. 752 62

Type 1 diabetes mellitus is associated with decreased insulin-like growth factor-1 (IGF-1) levels, enhanced values of growth hormone (GH) and IGF-binding protein 1 (IGFBP-1). Since the liver is the major source of IGF and IGFBP production, we have therefore examined whether levels of IGFs (IGF-1 and IGF-11) and IGFBPs (IGFBP-1 and IGFBP-3) differ when insulin is infused into the portal or peripheral vascular system. IGF, IGFBP, and GH levels were determined within 1-3 weeks of diagnosis in 36 patients (ranging in age from 18 to 22 years) with Type 1 diabetes mellitus. IGF-1 levels were low before insulin therapy administration (0.49 +/- 0.05 vs. 1.11 +/- 0.04 U/ml in controls, P < 0.01). With insulin treatment, IGF-1 levels rose to the normal range and IGF-1 normalisation depended on diabetes control and the route of insulin infusion. Diabetic patients with conventional insulin therapy (CIT; n = 12) had low IGF-1 (0.57 +/- 0.07 U/ml) compared with patients with continuous subcutaneous insulin infusion (CSII; n = 12; 0.75 +/- 0.08 U/ml; P < 0.05) and intraportal insulin infusion (IPII; n = 12; 1.07 +/- 10.05 U/ml; P < 0.05). Significant correlations were found between IGF-1 and parameters of glycemic control: HbA1c (r = -0.64; P < 0.01) and glycemia (r = -0.56; P < 0.05). The pattern of changes in IGF-11 levels was not significantly different from that of controls and was not altered by insulin therapy (0.98 +/- 0.08 and 1.01 +/- 0.04 U/ml in controls). Measured fasting 08:00 h IGFBP-1 levels were elevated 3-fold and IGFGP-3 levels were 2-fold lower in diabetic patients than in controls. Elevated IGFBP-1 levels were significantly correlated with metabolic control (glycemia, r = 0.64, P < 0.01; HbA1c, r = 0.71, P < 0.01). The mean elevated GH level before insulin administration (13.4 +/- 0.9 mg/l) was decreased by intensified insulin therapy (CSII, 8.8 +/- 0.6, P < 0.05; IPII, 5.6 +/- 0.9 mg/l, P < 0.001). There was a negative correlation between GH and IGF-1 (r = -0.72, P < 0.01). These results show the role of glycemic control and the route of insulin administration in the normalisation of IGF-1, IGFBP-1 and GH up to non-diabetic controls in patients with recent-onset Type 1 diabetes mellitus.
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PMID:Insulin-like growth factors and binding proteins in patients with recent-onset type 1 (insulin-dependent) diabetes mellitus: influence of diabetes control and intraportal insulin infusion. 753 Jun 21

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

Growth hormone binding proteins, insulin-like growth factor I and insulin-like growth factor binding proteins were determined in 54 children and adolescents affected by type 1 diabetes mellitus (25 prepubertal and 29 pubertal) showing reduced height velocity and the results were compared to those of 104 matched controls. Growth hormone binding proteins were similar in prepubertal and pubertal subjects but were significantly lower in the prepubertal diabetic group than in controls. Insulin-like growth factor I was low both in prepubertal and pubertal diabetic subjects. Insulin-like growth factor binding protein 3 was similar to controls, while insulin-like growth factor binding protein 1 and 2 were always high in diabetic children. Insulin-like growth factor binding protein 4 was high only in the prepubertal diabetic group. In conclusion, a low insulin-like growth factor I in diabetic children seems to depend on a GH receptor and/or a postreceptor defect. A low insulin-like growth factor I together with a normal insulin-like growth factor binding protein 3 and high levels of insulin-like growth factor binding proteins 1, 2 and 4 results in a reduced bioavailability of insulin-like growth factor I to target tissues. This could be a possible contributing factor to the reduced height velocity seen in our diabetic children.
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PMID:Growth hormone-binding proteins, IGF-I and IGF-binding proteins in children and adolescents with type 1 diabetes mellitus. 905 Sep 49

The aim of this study was to assess the GH-IGFI axis, GH receptor availability, as reflected by the levels of GH-BP, and the amount of GH-dependent IGFBP-3 in adult IDDM patients with different degrees of metabolic control. Thus, 10 adult well-controlled IDDMs (HbA1 7.8 +/- 0.4%), 10 adult non-ketotic poorly controlled IDDMs (HbA1 13.3 +/- 7%) and 14 sex- and age-matched healthy controls were subjected to two intravenous GH-RH stimulation tests with 0.1 and 1.0 microg/kg body weight respectively, and a plasma IGF-1 generation test induced by the administration of hGH. Poorly controlled IDDM patients exhibited an exaggerated GH response to 1.0 microg/kg of GH-RH when compared to healthy control subjects. Low fasting plasma IGF-1 levels and a blunted IGF-1 response to exogenously administered hGH were also found in poorly controlled IDDMs when compared to the healthy control group. GH-BP levels were significantly lower in IDDMs than in normal controls, and correlated positively with the IGF-1 generation capacity after hGH. Serum IGFBP-3 levels measured by RIA were similar in IDDM and control groups. Good glycemic control for 5.7 +/- 0.9 months did not correct the above mentioned abnormalities of the GH-IGF-1 axis. Our findings suggest that IDDM is associated with a diminished availability of GH receptors and synthesis of IGF-1. GH might then increase as a compensatory mechanism, further down-regulating liver GH receptors, and thus perpetuating the initial abnormality.
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PMID:Growth hormone-insulin-like growth factor-I axis in adult insulin-dependent diabetic patients: evidence for central hypersensitivity to growth hormone-releasing hormone and peripheral resistance to growth hormone. 993 Jun 32

The growth hormone (GH)-insulin-like growth factor (IGF) axis and insulin are major anabolic effectors in promoting weight gain and linear growth. These two anabolic systems are interlinked at many levels, thus abnormalities in one of these systems effect the other causing disordered metabolic homeostasis. Insufficient portal insulinization in insulin dependent diabetes mellitus (IDDM) results in hepatic GH resistance and increased production of IGF-binding proteins-1 (IGFBP-1) and IGFBP-2. GH resistance is reflected by decreased hepatic IGF-I production. In addition, changes in other GH-dependent proteins are also observed in IDDM. Increased proteolysis of IGFBP-3 results in reduction of intact IGFBP-3. Serum ALS levels are also slightly diminished in untreated diabetic patients. Hepatic resistance to GH is, at least in part, caused by diminished GH receptors as reflected by diminished circulating GHBP levels. In addition, there is also evidence from experimental and human studies suggesting post-receptor defect(s) in GH action. As a result of these changes, circulating total and free IGF-I levels are decreased during insulinopenia. Lack of negative feed-back effect of IGF-I on GH secretion causes GH hypersecretion which increases hyperglycemia by decreasing sensitivity to insulin. GH hypersecretion in poorly controlled diabetic patients may play a role in the pathogenesis of diabetic vascular complications. Most of these abnormalities in the GH-IGF axis in diabetes are reversed by effective insulinization of the patient. Addition of IGF-I treatment to insulin in adolescents with IDDM allows correction of GH hypersecretion, improves insulin sensitivity and glycemic control, and decreases insulin requirements. The effect of IGF-I treatment on diabetic complications has yet to be seen.
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PMID:Alterations in the growth hormone-insulin-like growth factor axis in insulin dependent diabetes mellitus. 1022 99

Insulin-like growth factor-I (IGF-I) enhances insulin action in normal subjects and in patients with both type 1 and 2 diabetes; however, its administration is associated with significant side effects in a high percentage of patients. The coadministration of IGF binding protein-3 (IGFBP-3, the predominant IGF binding protein in serum) with IGF-I limits IGF-I inducible side effects, but it does not attenuate the ability of IGF-I to enhance protein synthesis and bone accretion; therefore, we determined whether IGF-I/IGFBP-3 would retain biological activity in type 1 DM and limit side effects associated with free IGF-I administration. Twelve patients received recombinant human IGF-I plus IGFBP-3 (2 mg/kg-day) by continuous sc infusion for 2 weeks. Each subject served as his own control; and, during a paired 2-week period, each received a placebo infusion. The order of the treatments was randomized. Subjects were placed on a constant caloric intake but were allowed to adjust insulin doses to maintain appropriate levels of glycemic control. Subjects measured blood glucose four times per day at home and kept a log of their insulin use. Frequent sampling for glucose, insulin, and GH was conducted during four inpatient study periods, one at the beginning and one at the end of each 2-week study interval. During IGF-I/IGFBP-3, insulin doses were reduced by 49%, and mean serum glucose was reduced by 23%. Free insulin levels obtained during frequent sampling in hospital fell 47% on IGF-I/IGFBP-3, compared with control, but showed no change with placebo. Concomitant glucose measurements did not differ in the two treatment groups. There was no change in body weight. Fructosamine levels decreased by 12%, but this was not significant (P < 0.1). Fasting triglyceride was unchanged, but cholesterol declined from 170 +/- 24 to 149 +/- 31 mg/dL (P < 0.05). IGFBP-2 (an IGF-I-dependent responsive variable) rose from 141 +/- 56 to 251 +/- 98 ng/mL (P < 0.01) on IGF-I/IGFBP-3. To analyze the mechanism by which IGF-I/IGFBP-3 might reduce insulin requirements, the change in serum GH was quantified. Mean GH levels were reduced by 72%, from 2.48 to 0.55 ng/mL (P < 0.001). An equal number (40%) of drug- and placebo-treated subjects had minor hypoglycemic episodes at home that required adjustment of insulin doses. No episode was classified as severe. In contrast to previous studies with free IGF-I, there were no cases of edema, headache, jaw pain, retinal edema, or Bell's palsy. No subject withdrew because of drug complications. These findings indicate that IGF-I/IGFBP-3 is biologically active on carbohydrate metabolism, as measured by a decrease in insulin requirements in patients with type 1 diabetes. Further studies will be required to determine the long-term safety and efficacy of this combination in patients with insulin resistance and diabetes.
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PMID:The combination of insulin-like growth factor I and insulin-like growth factor-binding protein-3 reduces insulin requirements in insulin-dependent type 1 diabetes: evidence for in vivo biological activity. 1077 Jan 91

Diabetes mellitus and glucose dysregulation have significant effects on the circulating level of insulin-like growth factor-I (IGF-I) and IGF binding proteins (IGFBPs). In the present study, serum and urine IGFBP (IGFBP-1, -2, and -3) and serum IGF-I and -II levels were measured by radioimmunoassay (RIA) in 27 patients with type 1 diabetes aged 9 to 48 years compared with 9 healthy subjects aged 10 to 28 years. The patients were divided into 3 groups according to the amount of albumin excreted in 24 hours. The macroalbuminuria group (>500 mg/24 h) had elevated serum IGFBP-1 and -2 and decreased IGF-I levels (P < .01 v normal controls). Serum IGFBP-3 and IGF-II were not different among the patient groups and controls (P > .05). The mean urinary IGFBP-1 was decreased in all 3 patient groups compared with the controls (P < .05). Urinary IGFBP-2 and IGFBP-3 were increased in patients with macroalbuminuria. Immunoblot analysis showed increased low-molecular-weight fragments of urinary IGFBP-2 in the poorly controlled diabetics, and direct evidence for increased urinary IGFBP-2 proteolytic activity could be demonstrated in both the microalbuminuric and macroalbuminuric groups. Low-molecular-weight fragments of urinary IGFBP-3 were also increased in both the microalbuminuric and macroalbuminuric groups. In conclusion, alterations of IGFBPs in urine and serum are related to metabolic control in diabetic patients, and there is an increase of urinary IGFBP-2 protease activity in poorly controlled diabetics. The changes in serum IGFBP concentrations (eg, increases in IGFBP-1 and IGFBP-2) may lead to alterations in the availability of IGF-I to peripheral tissues.
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PMID:Insulin-like growth factor binding proteins (IGFBPs) in serum and urine and IGFBP-2 protease activity in patients with insulin-dependent diabetes mellitus. 1083 Nov 74

It has been hypothesized that a decreased amount of the free form of insulin-like growth factor-I (fIGF-I) results in morning hyperglycemia in patients with type 1 diabetes mellitus. In this study, we attempted to clarify the role of fIGF-I in relation to total IGF-I (tIGF-I) and its related peptides or proteins in type 1 diabetes. Forty-seven patients with type 1 diabetes, mean age 13.7 years, were evaluated. Blood samples were obtained for the measurement of BG at 0200, 0400 and 0700, and of insulin, total IGF-I (tIGF-I), fIGF-I, IGFBP-1 and IGFBP-3 at 0700. The SD scores (SDS) were determined for the levels of tIGF-I, flGF-I, IGFBP-1 and IGFBP-3 by using Japanese reference data. The morning increase in BG (deltaBG(4-7)) correlated significantly with fIGF-I SDS (r=-0.352, p=0.0152) and IGFBP-1 SDS (r=0.438, p=0.0021), but did not correlate significantly with the fIGF-I level itself or the ratio of fIGF-I to tIGF-I (f/t IGF-I ratio). Hereupon, the f/t IGF-I ratio correlated positively with fIGF-I SDS (r=0.541, p=0.0003). The mean+/-SD in the f/t IGF-I ratio was 0.94+/-0.43%, and that in fIGF-I SDS was -0.50+/-1.32. The level of IGFBP-I SDS correlated negatively with fIGF-I SDS (r=-0.472, p=0.0008) and insulin (r=-0.365, p=0.0116). We suggest that the morning level of fIGF-I SDS, rather than the fIGF-I level itself, may be a useful marker of decreased insulin-like bioactivity in the dawn phenomenon in type 1 diabetes mellitus.
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PMID:A role of free insulin-like growth factor-I in dawn phenomenon in children and adolescents with type 1 diabetes mellitus. 1089 Jan 93


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