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

The regulation of circulating insulin-like growth factor-binding protein-2 (IGFBP-2) in humans is not well understood. In vitro and animal data have identified the role of insulin in the regulation of IGFBP-2, but such a relationship has not been established clearly in humans. In the present study, serum IGFBP-2 concentrations were assessed by Western ligand blot and immunoblot analysis in children with newly diagnosed and untreated insulin-dependent diabetes mellitus (IDDM) and maturity-onset diabetes of the young before and at various times after insulin therapy. For comparison, IGFBP-2 levels were also determined in lean and obese age-matched controls. Children with IDDM were grouped according to their serum bicarbonate levels at the time of presentation (group A, > 20; group B, 13-20; group C, < 13 milliequivalents/L). Densitometric analysis demonstrated that before insulin therapy, group A patients had serum IGFBP-2 levels comparable to those in lean controls, and no significant change in IGFBP-2 was observed during insulin therapy. However, group B patients had a 2-fold elevation in IGFBP-2 levels before insulin therapy compared to lean controls. In these patients, IGFBP-2 tended to decrease at 1 week, but was not significantly reduced until 1 month after the initiation of insulin therapy. Group C patients had a 2.5-fold elevation of IGFBP-2 before treatment, which normalized by 1 month after treatment. Children with maturity-onset diabetes of the young, who had insulin levels and body mass indexes greater than IDDM patients and lean controls, had significantly lower IGFBP-2 levels than both lean and obese controls. IGFBP-2 levels tended to decrease further during insulin therapy. These results indicate that long standing alterations in serum insulin concentrations beyond the physiological range have significant influence on serum IGFBP-2 levels in children and confirm earlier findings that serum IGFBP-2 levels are not acutely regulated by insulin.
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PMID:Insulin-like growth factor-binding protein-2 and insulin: studies in children with type 1 diabetes mellitus and maturity-onset diabetes of the young. 853 Jun 14

Sex hormone binding globulin (SHBG) is normally decreased during puberty and inversely related to insulin resistance. Microalbuminuria is rare before puberty in Type 1 diabetes implicating that sex hormones may contribute to its development. We investigated SHBG levels in young females with > 5 years of Type 1 diabetes, and the association to microalbuminuria. Ten diabetic females with, and 15 without microalbuminuria, and 17 healthy controls in pubertal stage 4-5 were compared regarding anthropometric data, fasting serum levels of SHBG, testosterone, insulin, insulin-like growth factor-1 (IGF-1), lipids and lipoproteins. Multiple regression analyses were performed to study variables with independent influences on SHBG and albumin excretion rate (AER), respectively, in Type 1 diabetes. SHBG was lower and testosterone/SHBG ratio higher in normoalbuminuric females with diabetes than in controls. This was further emphasized in diabetic patients with microalbuminuria. IGF-1 was lower in Type 1 diabetes than in controls, and significantly decreased in microalbuminuric as compared to normoalbuminuric diabetic patients. IGF-1 was only correlated to SHBG in healthy controls. In Type 1 diabetes, applying stepwise multiple regression analysis, insulin dose, BMI, and HbA1c had a significant and independent inverse influence on SHBG (r2 = 0.77, p < 0.001). With log AER as the dependent variable, low SHBG, low IGF-1, HbA1c, and age added to the regression (r2 = 0.65, p = 0.004), whereas BMI, insulin dose and blood pressure did not. In conclusion, SHBG is decreased in young females with Type 1 diabetes, influenced by increased insulin requirements, BMI and HbA1c. In turn, low SHBG seems to be independently associated to elevated AER in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Indications of low sex hormone binding globulin (SHBG) in young females with type 1 diabetes, and an independent association to microalbuminuria. 854 43

Recombinant human insulin-like growth factor-1 (rhIGF-1) is currently used experimentally to treat patients with insulin-resistant diabetes mellitus, impaired growth, protein malnutrition, and osteoporosis. We report here the case of a marked transient alteration in consciousness in a healthy 22-year-old man who was given an IV infusion of a relatively low dose of rhIGF-1 for 1 hour. This individual developed the sudden onset of dizziness, nausea, coldness, air hunger, and pallor. He became unresponsive to simple questions and experienced diaphoresis, a feeling of warmth, and paresthesias. Although there was a mild fall in heart rate and blood pressure, these hemodynamic effects did not appear sufficient to cause the altered mentation. There were no changes in serum glucose, phosphorus, or potassium that could seem to account for these events. This individual recovered completely several minutes after stopping the rhIGF-1 infusion.
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PMID:Altered mental function during intravenous infusion of recombinant human insulin-like growth factor 1. 855 53

Parental genomic imprinting is the phenomenon in which the behavior of a gene is modified, depending on the sex of the transmitting parent [Peterson and Sapienza (1993): Annu Rev Genet 27:7-31]. Recent observations have revealed that the inheritance patterns, age-of-onset, severity, and etiology of certain human diseases can be explained by aberrations in the establishment or the maintenance of the imprint. Examples include the Prader-Willi, Angelman, and Beckwith-Wiedemann syndromes [Nicholls (1994): Am J Hum Genet 54:733-740], malignancy [Sapienza (1990): Biochim Biophys Acta 1072:51-61; Feinberg (1993): Nat Genet 4:110-113], and insulin-dependent diabetes mellitus (IDDM) [Julier et al. (1994) Nature 354:155-159; Bennett et al. (1995) Nat Genet 9:284-292]. We review the evidence that implicates an imprinted gene in the INS-IGF2 region of chromosome 11p15 in the etiology of IDDM (referred to as the IDDM2 locus) and show that in human fetal pancreas, INS is not imprinted, thus providing an argument against INS as the candidate gene. We also examine imprinting effects on the expression of IGF2 in components of the human immune system believed to be important in IDDM and show imprinted expression in fetal thymus as early as 15 weeks gestation. We demonstrate further that in the circulating mononuclear cells of two individuals, lectin-stimulated IGF2 transcription was biallelic, indicating relaxation of imprinting, whereas in one individual, transcription was monoallelic. Finally, we review the current available data supporting a role for insulin-like growth factor-II (IGF-II) in the immune system and, more specifically, discuss the evidence supporting a role for the IGFs in the prevention of apoptosis. These data have led us to formulate a novel hypothesis that could mechanistically explain the involvement of the IDDM2 locus in the pathogenesis of IDDM.
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PMID:Imprinting of IGF2, insulin-dependent diabetes, immune function, and apoptosis: a hypothesis. 856 31

To determine the effect of glycemic control on linear growth in children with insulin-dependent diabetes mellitus type 1, we studied 82 patients (40 male, 42 female) over a 6-year period. The mean +/-SD for age of onset and duration of IDDM were 7.3 +/- 3.9 years and 4.8 +/- 3.5 years, respectively. At each clinic visit, glycemic control was assessed by measuring glycosylated hemoglobin (GHb). For a total of 751 clinic visits, the mean +/- SD for chronologic age and GHb were 11.5 +/- 3.8 years and 10.2% +/- 2.3%, respectively. Good glycemic control was correlated with more frequent clinic visits (r= 0.219, P < 0.05). Growth was assessed by determining both weight and height, which were normalized for age and sex by calculating Z scores for weight and height and GHb. Moreover, regression analysis revealed no significant correlation between GHb levels and delta Z for either weight or height. While a significant correlation was observed between delta Z for weight and height (r = 0.30, P < 0.01), the relationship was not affected by glycemic control. Therefore, these data demonstrate that weight gain and growth rate do not seem to be significantly affected by glycemic control. This study also confirms that linear growth velocity is dependent on weight gain and suggests that in type 1 children, weight gain and level of growth-producing hormones such as insulin-like growth factor-1 (IGF-1) are more important regulators of linear growth than glycemic control.
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PMID:Does glycemic control affect growth velocity in children with insulin-dependent diabetes mellitus. 859 Jul 82

Experimental diabetes is associated with renal enlargement and glomerular hyperfiltration. Possible mechanisms for these changes could be the direct effects of growth factors such as insulin-like growth factor-1 and angiotensin II. We investigated whether treatment with trandolapril, an angiotensin converting enzyme inhibitor, prevented renal enlargement in streptozotocin-diabetic rats. Seven groups of male Wistar rats were studied: C (control + placebo); CL (control + low-dose trandolapril, 0.01 mg.kg-1.day-1); CH (control + high-dose trandolapril, 0.5 mg.kg-1.day-1; DP (diabetic + placebo); DI (diabetic, insulin-treated); DL (diabetic + low-dose trandolapril); DH (diabetic + high-dose trandolapril) and DI (diabetic + insulin). From day 2 glucose concentrations and body weight were similar in the non-diabetic and diabetic animals treated with insulin. Diabetic animals treated with placebo and low-dose trandolapril weighed significantly less compared to the control group. The diabetic groups, not treated with insulin, showed marked hyperglycaemia throughout the study. Kidney weight was greater in the diabetic, non insulin-treated groups compared with the control and insulin-treated groups. After 24 h of diabetes, kidney insulin-like growth factor-1 content was significantly increased from baseline levels in groups DP, DL and DH but by 48 h these levels had returned to normal. Renal tissue angiotensin converting enzyme activity was similar in groups C and DI but significantly reduced in all trandolapril-treated animals. Despite inhibiting renal angiotensin converting enzyme activity renal enlargement with increased tissue insulin-like growth factor-1 still occurred. This suggests that neither angiotensin II nor glomerular hyperfiltration, with raised intraglomerular pressure, play a role in the initial renal enlargement seen in experimental diabetes. Renal accumulation of insulin-like growth factor-1 appears to be an important factor in early renal hypertrophy and its effects are not modulated by angiotensin converting enzyme or angiotensin II.
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PMID:Renal enlargement and insulin-like growth factor-1 accumulation in the Wistar rat model of experimental diabetes is not prevented by angiotensin converting enzyme inhibition. 863 68

Insulin-like growth factor II (IGF-II), a member of the insulin family, regulates cell growth and differentiation. The IGF-II gene is localized close to the insulin gene in man and rat. IGF-II peptide binds weakly to the insulin receptor and exerts insulin-like effects on the blood glucose level. We studied IGF-II in endocrine pancreas in an animal model of noninsulin-dependent diabetes mellitus, the Goto-Kakizaki (GK) rat. At the age of 2 months, these rats have structural islet changes, with fibrosis and irregular configuration, so-called starfish-shaped islets. Immunohistochemical investigation revealed IGF-II immunoreactivity in the beta-cells in both GK and control rats. Pancreatic extraction, followed by size separation using gel chromatography, disclosed a high mol wt form of IGF-II in all animals, and RIA measurements revealed a considerably larger amount of the IGF-II peptide in the 2-and 6-month-old GK rats than in the 1-month GK and control rats. In situ hybridization of 3-month-old GK rats showed increased IGF-II messenger RNA expression in the starfish-shaped islets of GK rats than in the islets with normal structure in both diabetic and control animals. The reason for the increased amount of IGF-II is unclear. As the animals are diabetic before the islet changes occur, it might be a compensatory effect in response to hyperglycemia, but could also be a cause of the islet fibrosis.
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PMID:Increased amounts of a high molecular weight insulin-like growth factor II (IGF-II) peptide and IGF-II messenger ribonucleic acid in pancreatic islets of diabetic Goto-Kakizaki rats. 864 Nov 94

Diabetic neuropathy is a debilitating disorder whose causation is poorly understood. A new theory proposes that neuropathy may arise as a consequence of loss of neurotrophic insulin-like growth factor (IGF) activity due to diabetes, superimposed on a slow continual loss due to aging. The prediction that IGF-I and IGF-II gene expression are reduced in diabetic nerves was recently tested and validated. Here we tested the prediction that IGF administration can prevent or reverse diabetic sensory neuropathy. Subcutaneous infusion of IGF-I or IGF-II, but not vehicle, halted (P < 0.01) the progression of hyperalgesia in streptozotocin-diabetic rats. Moreover, impaired sensory nerve regeneration was partially reversed within 2 weeks after treatment of diabetic rats with IGFs (P < 0.01). Impaired regeneration could also be prevented by daily subcutaneous IGF injections. The low replacement doses of IGFs were effective despite unabated hyperglycemia and weight loss. These results show that IGF replacement therapy can reverse or prevent diabetic sensory neuropathy independently of hyperglycemia or weight loss.
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PMID:Insulin-like growth factors reverse or arrest diabetic neuropathy: effects on hyperalgesia and impaired nerve regeneration in rats. 869 62

Patients with acromegaly have significant morbidity and mortality, associated with cardiovascular disease. Acromegaly is often complicated by other diseases such as diabetes mellitus, hypertension, and coronary artery disease, so the existence of acromegalic cardiomyopathy remains uncertain. Cardiac performance was investigated in patients with uncomplicated acromegaly. A subgroup of hypertensive acromegalics was also studied. In addition, the effects of chronic octreotide therapy or surgery on cardiac structure and function in acromegaly were studied. Twenty-six patients and 15 healthy controls underwent gated blood-pool cardiac scintigraphy and echocardiography at rest and during exercise. Echocardiography was repeated after 6 months of octreotide therapy (n = 11). Cardiac scintigraphy was repeated after 12 and 24 months of octreotide therapy (n = 10) or 12 to 24 months after surgery (n = 8). ECG, blood pressure, and heart rate were monitored during cardiac scintigraphy. Left ventricular mass (LVM) was calculated from the findings of the echocardiography. Serum growth hormone (GH) levels and plasma insulin-like growth factor-1 (IGF-1) levels were monitored. LVM index was significantly higher (P < .003) in acromegalics than controls and in hypertensive acromegalics than normotensives, but all other indices of cardiac function were similar. Chronic octreotide decreased GH and IGF-1 levels and improved the structural abnormalities as measured by echocardiography. Chronic octreotide or surgery did not alter cardiac function parameters. Thus, important changes in cardiac structure and function occur in uncomplicated acromegaly, and improvements can be demonstrated after chronic octreotide therapy. Heart disease in acromegaly appears to be secondary to high circulating GH levels.
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PMID:Cardiovascular aspects in acromegaly: effects of treatment. 876 83

Major findings with regard to the somatostatin-growth hormone (GH)-insulin-like growth factor (IGF-1) axis and diabetes are summarized. GH hypersecretion and reduced circulating IGF-1 levels are prevalent in insulin-dependent diabetes. Somatostatin improves metabolism in insulin-dependent diabetics. Insulin resistance and poor metabolic regulation, which may partly be due to hypersecretion of GH, are believed to accelerate the development of diabetic angiopathy. Diabetic hypersomatotrophinemia may be due to hepatic resistance to GH and increased hepatic production of IGF-1-binding protein-1 (IGFBP-1), leading to reduced levels of circulating IGF-1 and further stimulation of GH production. Studies in vitro and in diabetics suggest a causal link between diabetic hypersomatotrophinemia and diabetic angiopathy. In vitro evidence for the involvement of IGF-1 in diabetic angiopathy is reviewed. Also reviewed is evidence, from rat and human studies, of the possible involvement of GH and IGF-1 in diabetic nephropathy. The role of somatostatin in late diabetic vascular complications remains to be elucidated.
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PMID:Somatostatin, growth hormone, insulin-like growth factor-1, and diabetes: friends or foes? 876 94


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