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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nephropathy, one of the major complications of diabetes mellitus, is characterized by an early increase in kidney size. In experimental models of diabetes, this event is preceded by a rapid and transient rise in kidney IGF-I levels, at least in adult animals. Since diabetes-associated renal changes are uncommon in young patients, we investigated the early changes in the components of the IGF system following induction of diabetes in prepubertal and postpubertal rats. The rationale for this study was the evaluation of potential differences which could lead to kidney complications only at adult stages. Unlike the situation in the postpubertal kidney, in which there was a transient accumulation of extractable IGF-I 24-48 h after streptozotocin (STZ) administration, there was a decrease of approximately 12-fold in the level of IGF-I in the prepubertal kidney over the same period of time. Paradoxically, kidney IGF-I mRNA levels were reduced by approximately 50% in the postpubertal rat 24 h after STZ treatment, whereas in the prepubertal kidney IGF-I mRNA levels were unaltered. Furthermore, the levels of IGF-I receptor mRNA and 125I-labelled IGF-I binding to kidney membranes of postpubertal diabetic rats were similar to the levels in control kidneys. On the other hand, both the levels of IGF-I receptor mRNA and 125I-labelled IGF-I binding were increased (approximately 2.5-fold (after 24 h) and approximately 3-fold (after 48 h) respectively) in prepubertal animals. In addition, increased expression of IGF-binding protein (IGFBP)-1 mRNA was seen early in diabetes in both pre- and postpubertal rats. The results of this study suggest that the transient accumulation of IGF-I in the kidney of the postpubertal diabetic rat may not be due to an increase in the local synthesis of IGF-I, but rather to an increase in IGF-I uptake from the circulation due to non-membrane-associated IGFBP-1. The lack of accumulation of IGF-I in the prepubertal kidney probably reflects the approximately 10-fold lower levels of circulating IGF-I in young as compared with adult diabetic rats.
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PMID:Differential accumulation of insulin-like growth factor-I in kidneys of pre- and postpubertal streptozotocin-diabetic rats. 752 Feb 45

Insulin-dependent diabetes can be associated with low insulin-like growth factor-I (IGF-I) levels despite normal or even high GH secretion. The basis of the diabetic abnormalities in GH-IGF dynamics that contribute to insulin resistance and impaired fuel metabolism are not well understood. To further investigate these matters, this study evaluated baseline IGF system parameters and responses to recombinant human IGF-I in four diabetic adolescents and six pubertal stage-matched controls. Spontaneous overnight and arginine-stimulated GH secretion, insulin, IGF-I, IGF-II, IGF-binding protein-1 (IGFBP-1), and IGFBP-3 levels were measured before, during, and after daily 10-h sc infusions of saline or IGF-I (20 micrograms/kg.h). Baseline overnight GH secretion and IGFBP-1 and -3 levels were not significantly different in the two groups, but IGF-I levels were significantly lower and IGF-II levels were higher in diabetic subjects. IGF-I infusion produced a 3-fold increase in serum IGF-I levels and a reciprocal profound reduction in IGF-II levels in both groups. IGFBP-1 levels increased dramatically in diabetics and modestly in normal subjects in response to IGF-I infusion, but IGFBP-3 levels were not significantly altered. Spontaneous overnight and arginine-stimulated GH secretion were suppressed by about 50% in both groups after IGF-I infusion. Insulin requirements were substantially reduced in diabetics receiving IGF-I, and insulin secretion was suppressed in normal subjects, with no evidence of a change in insulin half-life. Blood glucose remained stable in both groups throughout saline and IGF-I infusions, and no hypoglycemia or other adverse effect occurred during IGF-I infusions. Further studies are necessary to determine whether the addition of IGF-I to insulin replacement therapy may stably reduce the insulin requirement, maintain normal GH levels, and perhaps achieve better metabolic and anabolic balance in the treatment of insulin-dependent diabetes.
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PMID:The effects of subcutaneous insulin-like growth factor-I infusion in insulin-dependent diabetes mellitus. 752 24

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.
Diabetes Res Clin Pract 1994 Aug
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

The aim of the present study was to characterize the effect of 44 h of hyperglycaemia on diurnal levels of insulin-like growth factor binding protein-1 (IGFBP-1), insulin-like growth factor-1 (IGF-1), growth hormone (GH) and glucagon in 7 well-controlled subjects with insulin-dependent diabetes mellitus (IDDM). Hyperglycaemia (approximately 15 mmol/l) was induced by a glucose infusion, while the degree of insulinisation was similar to that of a corresponding period with near normoglycaemia (approximately 6.9 mmol/l). Hyperglycaemia for 44 h did not alter the normal diurnal IGFBP-1 levels when the degree of insulinisation was unchanged. The diurnal secretion pattern of IGFBP-1 was preserved in both genders and without any difference between the control and hyperglycaemic periods. However, the IGFBP-1 levels were increased in these IDDM subjects despite a peripheral hyperinsulinemia. An inverse correlation was found between IGFBP-1 and peripheral insulin levels both during periods of rapid changes in IGFBP-1 and insulin concentrations (i.e. morning hours) as well as during the total 24-h sampling period. Total IGF-1 levels were low, but no further decrease was seen after 24 h of hyperglycaemia in the presence of unchanged insulin levels. In conclusion, the present study clearly shows that the increased IGFBP-1 level seen during poor metabolic control in IDDM is not caused by hyperglycaemia. Glucose levels per se do not influence either total IGF-1 or IGFBP-1 concentrations in well-insulinised diabetic patients.
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PMID:Regulation of insulin-like growth factor binding protein-1 (IGFBP-1) in insulin-dependent diabetes mellitus. Effects of hyperglycaemia and insulin. 753 44

To further characterize the mechanism of impaired growth in children with insulin-dependent diabetes mellitus, we examined the serum components of the insulin-like growth factor (IGF) system in 11 children with new-onset insulin-dependent diabetes mellitus and followed the effect of insulinization on the IGF system longitudinally 1 day, 1 week, and 1 month after starting insulin treatment. Before insulin therapy, serum IGF-I, IGF-II, IGF-binding protein-3 (IGFBP-3), and GH-binding protein (GHBP) levels were significantly decreased, whereas IGFBP-1 and cortisol were significantly increased in diabetic children compared to those in an age-, sex-, and stage of puberty-matched control group. Random serum GH concentrations did not differ significantly. The alterations in the IGF system reversed with insulin therapy in a sequential manner. IGFBP-1 fell rapidly and was comparable to control values within 24 h after insulin treatment. IGF-I rose 1 week after treatment, reaching levels comparable to those in controls and continued to rise through 1 month of treatment. IGF-II, IGFBP-3, and GHBP showed a slower pattern of change, with their levels reaching control values only 1 month after the start of insulin treatment. Improvement in glycemic control, as determined by a change in hemoglobin-A1c, correlated positively with improvement in IGF-I, IGF-II, IGFBP-3, GHBP, and weight gain after 1 month of insulin therapy. These data are consistent with the hypothesis that changes in the IGF system in the insulinopenic state are similar to those during nutritional deprivation and may serve to minimize IGF's anabolic actions. The decreases in IGF-I, IGF-II, and IGFBP-3 may in part be due to a decrease in the GHBP/receptor. However, the observation that an increase in serum IGF-I was observed earlier than an increase in GHBP and without a significant change in serum GH suggests a direct stimulatory effect of insulin on liver IGF-I production or reversal by insulin of some postreceptor defect in GH action independent of GHBP.
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PMID:Effect of insulin on the insulin-like growth factor system in children with new-onset insulin-dependent diabetes mellitus. 753 5

The experiments reported herein were conducted to determine how corticosterone regulates growth and plasma insulin-like growth factor (IGF) I and IGF-binding protein (IGFBP) concentrations in normal and streptozotocin (STZ)-induced diabetic rats. Males were bilaterally adrenalectomized (Ax) or sham Ax and given intravenous injections of 0, 30, or 65 mg STZ per kg body wt (0, 30, or 65 STZ) to induce varying degrees of insulin deficiency and implanted with 100-mg pellets containing 0, 40, or 80% corticosterone in cholesterol. Changes in plasma IGFBP concentrations were determined by Western ligand blotting or immunoblots. Neither IGFBP-5 nor IG-FBP-6 was detected in any of the treatment groups. Plasma IGFBP-2 was elevated and IGF-I was reduced in the nondiabetic Ax rats compared with sham Ax controls, but plasma IGFBP-3 and -4 were not significantly changed. Adrenalectomy had no affect on tibial growth or plasma IGFBP-1 in these animals. Plasma IGF-I, IGFBP-1 and -3, and tibial growth were equal among 0, 30, and 65 STZ Ax rats that did not receive corticosterone. Plasma IGFBP-4 was inversely related to the amount of STZ injected in these animals, and IGFBP-2 was elevated in those given the high dose of STZ. In the 0 STZ Ax rats, plasma IGF-I and IGFBP-3 increased in proportion to the corticosterone implant dose, but IGFBP-1 was unaffected. By contrast, IGF-I and IGFBP-3 were unaltered by corticosterone in the 30 STZ Ax rats, and IGFBP-1 increased in proportion with the dose of corticosterone.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1995 Dec
PMID:Corticosterone regulation of insulin-like growth factor I, IGF-binding proteins, and growth in streptozotocin-induced diabetic rats. 758 49

Ovarian function in post-menarchal girls with Type 1 diabetes was evaluated. Menstrual histories from 24 adolescents with Type 1 diabetes were compared with those from 24 age and sex matched controls. A fasting blood sample was obtained from subjects with Type 1 diabetes for the measurement of ovarian and adrenal sex hormones, LH and FSH, glucose and insulin, insulin-like growth factor-I (IGF-I), and insulin-like growth factor binding protein-1 (IGFBP-1); and an ovarian ultrasound scan was performed. Menstrual irregularity was more prevalent in patients with Type 1 diabetes than controls (54% vs 21%, p < 0.01) and their mean body mass index (BMI) was greater (22.3 +/- 0.5 (+/- SEM) vs 20.7 +/- 0.6 kg m-2, p < 0.05). Subjects with Type 1 diabetes with irregular menses (when compared with diabetic subjects with a regular cycle) had a significantly higher HbA1 (12.8 +/- 0.4 vs 10.5 +/- 0.5%, p < 0.01) and BMI (23.2 +/- 0.6 vs 21.4 +/- 0.6 kg m-2, p < 0.05) associated with a lower sex hormone binding globulin (SHBG) (37.2 +/- 4.0 vs 52.6 +/- 4.0 nmol l-1, p < 0.025) and IGF-I (1.4 +/- 0.2 vs 2.2 +/- 0.2 mUI-1, p < 0.025) and a higher LH:FSH ratio (2.6 +/- 0.5 vs 1.4 +/- 0.2, p < 0.05). Polycystic ovarian changes were identified in 10/13 (77%) of these patients with an irregular cycle. Menstrual irregularity is common in post-menarchal girls with Type 1 diabetes and is associated with poor glycaemic control and weight gain. The apparent high incidence of polycystic ovarian change requires further investigation.
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PMID:Menstrual irregularities are more common in adolescents with type 1 diabetes: association with poor glycaemic control and weight gain. 808 24

Early renal manifestations of type I diabetes include kidney enlargement, increased glomerular filtration rate, and renal plasma flow. These hemodynamic changes may be caused by a number of factors, including growth hormone and/or insulin-like growth factor-I (IGF-I). Streptozotocin-induced insulinopenic diabetes in rats represents a model of human type I diabetes and is associated with the early hemodynamic changes in the kidney seen in poorly controlled type I diabetic patients. These changes are preceded by an accumulation of IGF-I peptide in the kidney. Insulin-like growth factor-I is not locally produced, but rather accumulates from circulating IGF-I, trapped by increased levels of IGF-binding proteins, particularly IGF-binding protein-1. The hemodynamic effects, reproduced by infusions of recombinant human IGF-I in normal rats, may be blocked by co-infusion of a kinin-receptor antagonist, suggesting that at least one of the mechanisms involved is the kallikrein-kinin system. These studies strongly support the notion that the IGF system may play a role in early hemodynamic manifestations of the diabetic kidney. Whether these effects lead to long-term diabetic renal disease remains to be studied.
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PMID:The role of insulin-like growth factors in diabetic kidney disease. 823 20

Growth hormone (GH) hypersecretion and relative insulin-like growth factor I (IGF-I) deficiency have been implicated in the development of insulin resistance, poor metabolic control, and impaired growth during puberty in insulin-dependent diabetes mellitus (IDDM). Portal levels of insulin are critical for the integrity of the hepatic GH receptor and suppression of the inhibitory IGF-binding protein I. Increasing insulin doses during puberty will result in adequate portal levels of insulin and thus restore IGF-I levels and IGF bioactivity, but at the risk of nocturnal hypoglycaemia and weight gain. Restoration of normal circulating levels of IGF-I using the recombinant peptide will lead to reductions in GH levels and improved insulin sensitivity. Given as a daily subcutaneous injection, low-dose recombinant human IGF-I (40 micrograms/kg/day) could prove to be a useful adjunct to standard insulin therapy during puberty in IDDM. The reduced and more stable insulin requirement might reduce the risks of nocturnal hypoglycaemia and weight gain. However, whereas intensified insulin therapy will reduce the risk of microangiopathic complications, the benefits of combination therapy have not been proven. The role of recombinant human IGF-I in the treatment of IDDM needs to be tested by long-term controlled trials.
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PMID:Growth hormone insulin-like growth factor I axis in insulin-dependent diabetes mellitus. 885 34

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


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