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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperglycemia, hyperinsulinemia, and insulin resistance cause vascular disease in type 2 diabetes mellitus. Dietary treatment alone often fails and oral drugs or insulin enhance hyperinsulinemia. In previous studies, an intravenous bolus of recombinant human insulin-like growth factor-I (rhIGF-I) caused normoglycemia in insulin-resistant diabetics whereas rhIGF-I infusions lowered insulin and lipid levels in healthy humans, suggesting that rhIGF-I is effective in insulin-resistant states. Thus, eight type 2 diabetics on a diet received on five treatment days subcutaneous rhIGF-I (2 x 120 micrograms/kg) after five control days. Fasting and postprandial glucose, insulin, C-peptide, proinsulin, glucagon, triglyceride, insulin-like growth factor-I and -II, and growth hormone levels were determined. RhIGF-I administration increased total IGF-I serum levels 5.3-fold above control. During the control period mean (+/- SD) fasting glucose, insulin, C-peptide, and total triglyceride levels were 11.0 +/- 4.3 mmol/liter, 108 +/- 50 pmol/liter, 793 +/- 250 pmol/liter, and 3.1 +/- 2.7 mmol/liter, respectively, and decreased during treatment to a nadir of 6.6 +/- 2.5 mmol/liter, 47 +/- 18 pmol/liter, 311 +/- 165 pmol/liter, and 1.6 +/- 0.8 mmol/liter (P < 0.01), respectively. Postprandial areas under the glucose, insulin, and C-peptide curve decreased to 77 +/- 13 (P < 0.02), 52 +/- 11, and 60 +/- 9% (P < 0.01) of control, respectively. RhIGF-I decreased the proinsulin/insulin ratio whereas glucagon levels remained unchanged. The magnitude of the effects of rhIGF-I correlated with the respective control levels. Since rhIGF-I appears to improve insulin sensitivity directly and/or indirectly, it may become an interesting tool in type 2 diabetes and other states associated with insulin resistance.
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PMID:Insulin-like growth factor-I improves glucose and lipid metabolism in type 2 diabetes mellitus. 146 83

Effects of two winter nutritional levels (LOW, MOD) and two summer pastures (bahiagrass, BG; perennial peanut, PP) on plasma IGF-I, and the relationship between IGF-I and average daily gain (ADG), thyroid hormones, plasma urea, packed cell volume (PCV) and steer type were determined in 101 steers (217 kg) varying in breed composition, frame size and initial condition. Relationships between body composition or composition of gain and IGF-I were determined in 11 contemporary steers assigned directly to the feedlot. Initial IGF-I (57.9 +/- 3.5 ng/ml) was positively correlated (P less than .05) to initial condition, estimated percentage of Brahman and plasma T3, but not related to subsequent ADG. During the 126-day wintering period, ADG was .21 kg for the LOW winter treatment and .47 kg for the MOD winter treatment. Concentration of IGF-I in the wintering period was affected (P less than .01) by nutritional level (LOW = 71.8 ng/ml, MOD = 150.6 ng/ml) and was positively related to winter ADG in MOD steers (P less than .01) but not in LOW steers. Concentration of IGF-I in winter was also positively related to condition at the end of the winter period (P less than .01), T3 (P less than .05) and T4 (P less than .05). There were no effects of winter treatment on IGF-I during the subsequent summer pasture period. During the 145-d summer period, ADG was .53 kg for BG and .68 kg for PP. Concentration of IGF-I during the summer period was affected (P less than .05) by pasture treatment (BG = 138.6 ng/ml, PP = 181.9 ng/ml), was positively related (P less than .01) to PCV and percentage of Brahman, and was negatively related (P less than .05) to estimated percentage of English breeding. In steers assigned directly to the feedlot, IGF-I was correlated with empty body (EB) weight (r = -.59, P less than .10), EB water (r = -.59, P less than .10) and EB protein (r = -.60, P less than .10) at slaughter, and with days on feed (r = -.65, P less than .05), but was not correlated with ADG or rate of component gain. These data indicate that IGF-I is related to nutritional status in steers as in other species, that there may be significant breed or cattle type differences in circulating concentrations of IGF-I, and that circulating concentration of IGF-I may be functionally related to plasma concentration of thyroid hormones.
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PMID:Effects of winter nutrition and summer pasture or a feedlot diet on plasma insulin-like growth factor I (IGF-I) and the relationship between circulating concentrations of IGF-I and thyroid hormones in steers. 226 59

The serum levels of 34K insulin-like growth factor (IGF)-binding protein were measured by RIA in 88 type 1 diabetic patients, 9 patients with type 2 diabetes, 7 patients with insulinoma, 19 normal subjects (all after an overnight fast), and 82 normal subjects after a breakfast meal. In addition, the effect of 2- to 3-h euglycemic steady state hyperinsulinemia on serum IGF-binding protein and IGF-1 levels was studied in some subjects in each of the fasted groups. Compared with normal subjects, the mean serum IGF-binding protein levels were 4-fold (P less than 0.001) higher in type I diabetic patients treated with conventional insulin injections, 2.5-fold (P less than 0.001) higher in those treated with continuous sc insulin infusion, and 2-fold (P less than 0.05) higher in patients with type 2 diabetes. In the patients with insulinoma, the mean IGF-binding protein level was 63% below normal (P less than 0.001), and it normalized after removal of the tumor. There was a slight negative correlation between the IGF-binding protein level and insulin dose in the diabetic patients (r = -0.22; P less than 0.05). In normal subjects, serum insulin concentrations were 2-fold higher (P less than 0.001) and the IGF-binding protein level was 29% lower after a meal (P less than 0.05) than in the fasting state. Serum IGF-I concentrations were virtually identical in the type 1 and 2 diabetic patients, insulinoma patients, and normal subjects. During steady state euglycemic hyperinsulinemia, the IGF-binding protein level fell by 40-70% in each group (P less than 0.001), whereas the IGF-I level declined (P less than 0.05) in the type 2 diabetic patients only. The decline of binding protein was closely related to the baseline level (r = 0.94; P less than 0.001). No correlation was found between serum IGF-I and binding protein levels in any group. In conclusion, 1) serum 34K IGF-binding protein levels are elevated in type 1 and 2 diabetic patients and decreased in patients with insulinoma; 2) the serum binding protein, but not IGF-I concentration is decreased by acute hyperinsulinemia; and 3) these data suggest that the serum insulin concentration plays a role in regulation of the serum 34K IGF-binding protein concentration.
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PMID:Insulin regulates the serum levels of low molecular weight insulin-like growth factor-binding protein. 244 29

We examined 125I-insulin-like growth factor I (125I-IGF-I) binding to erythrocytes from 24 normal and 21 non-insulin-dependent diabetic (NIDDM) subjects. 125I-IGF-I binding to human erythrocytes was specifically inhibited by unlabeled IGF-I, and Scatchard analysis indicated a curvilinear plot. There was a significant difference in IGF-I binding between normal and diabetic subjects (7.78 +/- 0.42 vs. 5.80 +/- 0.33%/2.4 x 10(9) cells/ml, P less than 0.001). Among diabetic patients, IGF-I binding to erythrocytes from those with retinopathy and those without retinopathy was comparable. These results suggested that decreased IGF-I binding might be a factor responsible for some pathological features such as delayed wound healing in diabetic patients.
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PMID:Insulin-like growth factor I receptors on erythrocytes in NIDDM. 253 1

Despite reports of reduced serum insulin-like growth factor (IGF) levels in experimentally diabetic animals, human diabetic patients have been reported to have decreased, normal, or even elevated levels. This study was a cross-sectional examination of the effect of age on immunoreactive IGF-I levels in adult patients with insulin-dependent or noninsulin-dependent diabetes mellitus (IDDM and NIDDM) attending a diabetes out-patient clinic. The patients and normal subjects studied were divided into the age ranges 21-30, 31-40, 41-50, 51-60, and over 60 yr. For all ages combined, the mean IGF-I level (+/- SD) was 0.84 +/- 0.26 U/ml (202 +/- 62 ng/ml) in 133 normal subjects, significantly reduced to 0.41 +/- 0.17 U/ml in 121 IDDM patients, and 0.49 +/- 0.19 U/ml in 46 NIDDM patients (both P less than 0.001). In both groups there was a marked decline in IGF-I with increasing age (P less than 0.01). Except for NIDDM patients aged 21-30 yr (only two patients), IGF-I levels in both IDDM and NIDDM patients were significantly lower in every age range than those in age-matched normal subjects, but did not differ between the two diabetic groups. Glycosylated hemoglobin levels correlated inversely with IGF-I levels only in younger patients with IDDM (r = -0.486; P less than 0.05 for patients aged 21-40 yr). We conclude that factors common to IDDM and NIDDM, perhaps related to relative nutritional deficiency at the cellular level, cause a reduction in serum IGF-I levels, and that this reduction occurs independently of age-related changes in IGF-I.
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PMID:Serum insulin-like growth factor I levels in adult diabetic patients: the effect of age. 373 35

It has been suggested that recombinant human IGF-I (rhIGF-I) is a potential therapeutic agent in diabetes mellitus. It is known to have glucose-lowering effects in normal individuals, in patients with non-insulin-dependent diabetes (NIDDM) and in extreme insulin-resistant states. IGF-binding proteins (IGFBPs) have the potential to affect the biological activity of rhIGF-I. We have studied the effect of infused rhIGF-I on IGFBP-1 and IGFBP-3 in a patient with Mendenhall's syndrome, a rare insulin-resistant state. During an infusion of 20 mg rhIGF-I, glucose concentrations fell from 44.1 +/- 7.2 to 31.5 +/- 7.2 (S.E.M.) mmol/l (P = 0.001), and insulin and C-peptide levels fell from 920 +/- 62 to 542 +/- 45 mU/l (P = 0.008) and 5466 +/- 633 to 3071 +/- 297 pmol/l (P = 0.02) respectively. Significant lowering of phosphate, magnesium and alkaline phosphatase concentrations was also noted. IGF-I levels rose from 48 +/- 10.2 to 410 +/- 50.1 micrograms/l (P = 0.001), and those of IGF-II fell from 279.8 +/- 8.3 to 104.3 +/- 7.9 micrograms/l (P = 0.001). IGFBP-1 concentrations did not significantly change during the infusion but those of IGFBP-3 increased from 1655 +/- 127 to 2197 +/- 334 micrograms/l (P = 0.002), despite a significant fall in GH concentrations from 10.7 +/- 2.6 to 4.1 +/- 1.1 mU/l (P = 0.007), suggesting that IGFBP-3 regulation is also IGF-I-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Response of insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) and IGFBP-3 to IGF-I treatment in severe insulin resistance. 751 62

Recent evidence suggests that a number of adulthood conditions, including non-insulin dependent diabetes mellitus (NIDDM) and lipid and cardiovascular abnormalities are associated with intra-uterine growth retardation (IUGR). It is possible that this arises from programming of endocrine axes during development as a result of an adverse intra-uterine environment. Insulin-like growth factors (IGFs) are mitogenic polypeptides which stimulate cellular proliferation and differentiation and are important in human fetal development. The functions of IGFs are modulated by specific high affinity binding proteins (IGFBPs). IGFBP-1 is antagonistic to the insulin-like and growth promoting effects of IGF-I, and IGFBP-3 holds IGFs in the circulation by associating with IGFs and an acid labile subunit to form a ternary complex. Using specific radioimmunoassays and fetal serum obtained during diagnostic cordocentesis we have investigated the role of the IGF/IGFBP axis in human fetal development. In a study of 130 singleton pregnancies we have examined levels of immunoreactive IGFs and IGFBPs in normally grown fetuses (AGA), starved small fetuses affected by uteroplacental insufficiency (UPI), and non-starved small fetuses (SGA). IGF-I was significantly lower in the UPI group (n = 14, 7.8 +/- 0.6 micrograms l-1), than in either the SGA group (n = 22, 31.4 +/- 3.5 micrograms l-1, P = 0.0001) or the AGA group (n = 94, 36.3 +/- 1.9 micrograms l-1, P = 0.0001). IGFBP-3 showed similar changes (UPI: 682.6 +/- 50.0 micrograms l-1; SGA: 831.9 +/- 55.5 micrograms l-1; AGA: 847.7 +/- 19.8 micrograms l-1).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The pathophysiology of the insulin-like growth factor axis in fetal growth failure: a basis for programming by undernutrition? 753 96

Growth hormone secretion is blunted in obesity. Recent studies have shown that the sub-group of obesity with preponderance of accumulation of fat in visceral depots is associated with endocrine abnormalities. We therefore measured IGF-I concentrations in serum in 27 men who also underwent computerized tomography measurements of regional and total body fat mass. Furthermore, euglycemic-hyperinsulinemic glucose clamps were used to determine insulin resistance, and established 'risk factors' for cardiovascular disease and non-insulin dependent diabetes mellitus were measured, i.e. blood pressure, plasma lipids, and blood glucose, as well as sex steroid hormones. Visceral fat mass systolic blood pressure and triglycerides were higher (P < 0.05) in the group with low (87 +/- 4 micrograms/l) IGF-I values, compared to those with high (126 +/- 6 micrograms/l) IGF-I values, divided after the median value. IGF-I was negatively correlated with visceral fat mass (r = 0.40), independently of subcutaneous and total fat mass. As described before visceral fat mass was directly associated to a majority of the measured 'risk factors', as well as indirectly to testosterone and sex hormone binding globulin (SHBG) concentrations. The latter were also strongly related statistically to the 'risk factors'. IGF-I concentrations showed, however, weaker correlations with the metabolic factors, blood pressure or sex steroid hormones. Multivariate analyses revealed that the correlations of visceral fat with the risk factors were not influenced by IGF-I, while testosterone or SHBG totally abolished these associations. The results indicate that low serum IGF-I concentrations, suggesting deficient growth hormone secretion, are associated with visceral but not with subcutaneous or total fat masses.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Low concentrations of insulin-like growth factor-I in abdominal obesity. 838 69

Insulin resistance is one of the major underlying abnormalities in NIDDM, however, its pathophysiologic mechanisms are not well understood. Many clues about the mechanisms of insulin action have come from patients with the most severe forms of insulin resistance, including those with genetic abnormalities in the insulin signal transduction cascade. We used rhIGF-I as a probe to differentiate insulin and IGF-I action and to study the therapeutic potential of IGF in states of insulin resistance. To date, we have studied six subjects with varying phenotypes of severe insulin resistance but without mutations in the insulin receptor itself. All subjects underwent baseline physiologic monitoring to quantitate carbohydrate tolerance, insulin secretion, and insulin action prior to receiving rhIGF-I at 100 micrograms/kg body wt s.c. bid for 1 month with interval testing of glycemic control and insulin sensitivity. None of the six subjects noted significant side effects from the rhIGF-I. Four of the six subjects had overt diabetes during control testing; three of these subjects demonstrated normalization of fasting and postprandial blood glucose concentrations during rhIGF-I administration on no other therapy. In the fourth patient, insulin requirements and fasting hypertriglyceridemia decreased without improvement in glycemic control. The two subjects with normal glucose tolerance (two sisters with congenital lipodystrophy) maintained normal glucose tolerance at dramatically lower insulin levels and had a dramatic reduction in triglyceride levels. The efficacy of IGF-I continued to increase over the duration of the study.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin-like growth factor I (rhIGF-I) as a therapeutic agent for hyperinsulinemic insulin-resistant diabetes mellitus. 852 13

Insulin-like growth factors (IGF-I and IGF-II) are produced in most tissues, particularly liver. Via endocrine and paracrine or autocrine mechanisms, they play an essential role in cell proliferation and differentiation and complement the metabolic effects of insulin. Similarities between the effects of insulin and IGF in vitro are largely due to cross-reaction, owing to their structural homology as well as that of their receptors. At physiological concentrations, insulin is not mitogenic. Compared with insulin, IGFs have negligible metabolic effects on hepatocytes or adipocytes. However, the presence of the IGF-I receptor in muscle accounts for IGF physiological effects in vivo on glucose uptake and glycogen synthesis. Moreover, recombinant IGF-I administered subcutaneously to healthy subjects or patients with Type 2 diabetes causes a drop in plasma levels of triglycerides and VLDL as well as cholesterol and LDL, but not HDL, and also increases insulin sensitivity. All these responses reflect IGF-I inhibition of insulin and GH secretion. In biological media, IGF-I and IGF-II are reversibly associated with specific high-affinity (10(9)-10(11) M-1) binding proteins (IGFBP-1 to -6) differing in expression according to tissue of origin and playing a variety of roles in IGF transport and half-lives, delivery of IGFs to their target cells and modulation of IGF interactions with their receptors. In the blood, where IGF concentrations are 1,000 times those of insulin, IGFBP-3 (the major form) binds at least 80% of IGFs as 140-kDa complexes which do not cross the capillary endothelium and therefore prevent the insulin-like action of IGFs. Nevertheless, these circulating IGF reserves may be mobilized in response to metabolic needs via limited proteolysis of IGFBP-3 by serine proteases. In the case of IGFBP-1, whose hepatic synthesis is negatively regulated by insulin, plasma concentrations are subject to extensive nycthemeral variation, rising with fasting and dropping after feeding, which may be involved in controlling the access of free IGF-I to its cellular receptors and hence IGF-I-regulated glucose and amino acid uptake. Therapeutic applications of recombinant human IGF-I, currently under trial in the treatment of growth retardation resulting from GH receptor abnormalities, hypercatabolic states and would repair, may also be envisaged for cases of insulin resistance, particularly type 2 diabetes.
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PMID:The IGF system in metabolism regulation. 858 49


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